TW201247612A - Compositions for treating kidney disorders - Google Patents

Abstract

The present invention provides methods for treating glomerulosclerosis such as focal segmental glomerulosclerosis (FSGS) or glomerulonephritis such as immunoglobulin A nephropathy (IgAN) by cyclohexenone compounds.

Description

201247612 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to a method for treating glomerulosclerosis or glomerulonephritis, and particularly for treating a cyclamate compound such as localized glomerulosclerosis Method for kidney glomerulosclerosis or renal glomerulonephritis such as immunoglobulin type A glomerulonephritis This application claims to be filed on January 21, 2011, US application No. 61/4352 (nicknamed and in 2011 10 US Application No. 6i/5449i, nicknamed on the 7th of the month, and its contents are incorporated herein by reference. [Prior Art] Many diseases or defects affect kidney function by attacking the kidney skein. Diseases include many diseases caused by a variety of genes and environmental factors' but are mainly divided into two categories: glomerulosclerosis and glomerulonephritis. Kidney sclerosing refers to glomerular sclerosis in the renal pelvis. Refers to the microvessels of the kidney, (4) balls, and the function of the kidneys used to filter urine from the blood. The protein (the most abundant protein in the urine) is the spheroidal hardening 's. Kidney damage affects the kidney filter. Features And cause the protein to leak into the urine. The glomerular sclerosis is only the cause of many urinary proteins. The kidney section may be a judgment of whether the patient suffers from skein of the kidney. Renal spheroidal hard sputum can be referred to as local glomerulosclerosis (FSGS) and nodular kidney 3 201247612 Local glomerulosclerosis (FSGS) is local squamous cell sclerosing and podocyte foot flattening The damage characteristics of the foot process effacemen are judged. Nearly 20 years of research have shown that the incidence of end stage renal disease in patients with FSGS is between 13 and 78%. Although the cause and pathogenesis of FSGS are not clear, but mainly It should be caused by the damage of the glomerular epithelial cells themselves, which leads to the complex reaction of the kidney spheroids, which leads to the hardening of the kidney. The nodular glomerulosclerosis or intercapillary glomerulonephritis can also be called It is a diabetic nephropathy (diabetic nephropathy) or Kimmelstiel-Wilson syndrome, which is a progressive kidney and is caused by capillary disease of the glomerulus. The disease is characterized by nephropathy. And diffuse glomerular sclerosis; and caused by diabetes for a long time, and the main treatment in each country is dialysis. Up to now, although steroids and immune preparations are mainly used to treat primary FSGS, this The therapeutic effects of these therapies on the development of renal injury are still wired, and because of the various side effects, the treatment is based only on rule of thumb and less on pathological evidence (see Matalon, et al., Semin Nephrol, 20: 309-317, 2000; Braun, et al., Cochrane Database Syst Rev: CD003233, 2008) ° Renal glomerulonephritis refers to the inflammatory response of the renal membrane tissue, in which the modular tissue has a filtering function and can be separated from the blood. Waste and more than Zhao. Among them, the most common renal glomerulonephritis is immunoglobulin A type glomerular nephritis (IgAN), the cause of this accelerated development of nephritis is still unpredictable, and it is still clinically impossible to prevent and treat, so it is considered as likely One of the main causes of kidney disease, spastic renal failure. Therefore, in the kidneys of patients with Ig AN, even if other immune, clinical, and pathological factors cause renal failure, systemic tau cell activation and lymphocytes/macrophages/neutrophils Abnormal increase in infiltration, etc., is considered to be one of the main processes leading to the conversion of IgAN into chronic renal failure (Kamei, et al., Clin. J. Am. Soc. Nephrol. 2011, 14; Chan, et al., Clin. Exp. Nephrol. 2004, 8:297-303; Chao, et al., Kidney Int. 70:283-297 (2006); , Lai, KN, 92:263-270 (2002)). Furthermore, oxidative stress is also a major cause of the increase and development of IgAN in patients and animal models; it has been reported that reactive oxygen species (ROS) are directly induced in most human and experimental kidney diseases (including IgAN). disease. Although glucocorticoid steroids have been widely used in the treatment of IgAN patients, their effects on IgAN's ability to maintain kidney function and slow down urinary protein remain unclear and potentially uncontrollable inhibition due to prolonged use. The side effects of the immune response still cause problems in medication. SUMMARY OF THE INVENTION One embodiment of the present invention provides a method for treating a kidney spheroid disease (eg, glomerulosclerosis or glomerulonephritis) of a subject, comprising: administering an effective dose of one of cycloheximide An enone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, or a prodrug thereof to the host, wherein the cyclohexenone compound has the following structure:

Wherein each of the X and Y systems is independently oxygen, nr5, or sulfur; 201247612 R is hydrogen or an alkyl group; each of R, R2, and R3 is independently hydrogen, methyl, or (CH2) m-CH3; R4 is NR5R6, OR5, OC(=〇)R7, c(=0)0R5, c(=o)r5, halogen, 5 or 6 membered ring lactone, CVC8 alkyl, c2-C8 olefin a C2-C8 alkynyl, aryl, or glucosyl group, wherein '5 or 6 membered ring lactone, CrCe alkyl, C2-C8 alkenyl' C2-C8 alkynyl, aryl, and glucosyl selective One or more selected from the group consisting of NR5R6, OR5, 〇C(=〇)R7, c(=o)or5, c(=o)r5, cvc8 alkyl, C2-C8 dilute, c2-c8 block, c3 Substituting -c8 cycloalkyl, C|-C8 haloalkyl, and C丨-C8 alkoxy substituent; each R·5, and R6 are each independently hydrogen or c丨-C8 alkyl; Is a Ci-C8 alkyl group, hydrazine R5, or NR5R6; m is 1-12; and Π is 1 -12. Another embodiment of the present invention provides a method of slowing renal function damage or renal pelvic damage in a subject, comprising: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite, a solvate thereof, or a prodrug thereof to the main genus, wherein the cyclohexanone compound has the following structure:

Wherein each of the X and γ systems is independently oxygen, NR5 ' or sulfur; R is hydrogen, or C(=0)C|-C8 alkyl; each R, R2, and R3 are each independently hydrogen , methyl, or (CH2)m_CH3 ; 6 201247612 Κ·4 is NR_5R6, 〇R5 ' 〇c(=0)R7, C!(=〇)〇R5, c(=o)r5, Nansu, 5 Or 6-membered ring lactone, CrCs alkyl, c2-c8 alkenyl, C2-C8 alkynyl, aryl, or glucosyl, wherein 5 or 6 membered ring lactones, C "C8 alkyl, C2-C8" One or more selected from the group consisting of C2.-C8, aryl, and glucosyl are selected from nr5r6, > 〇R5, 〇C(=〇)R7, C(=0)0R5, c(= o) substituted with a substituent of r5, C1-C8 alkyl, C2-C8 dilute, C2-C8 alkynyl, C3-C8 cyclohexyl, Ci-〇8 haloalkyl, and crc8 alkoxy; Each of r5 and Han 6 is independently hydrogen or c "c8 alkyl; cardiac cardio-alkyl, or5, or nr5r6; m is 1-12; and η is 1-12. Another embodiment of the present invention The method provides a method for increasing the activity of a renal cell nuclear factor-Ε2 correlation factor 2 (Nrf2) of a subject, comprising: administering an effective dose of one of the cyclohexanone compounds, and medicinally Acceptable salts of the type, a metabolite thereof, a solvate thereof, or the precursor of the drug to the body, wherein the cyclohexene compound is one having the following structure:

Wherein each X and Y system is independently oxygen, NR5, or sulfur; R is hydrogen or CPCOCVCs alkyl; each R丨, R2, and R3 are each independently hydrogen, methyl, or (CH2) m_CH3 ; R4 is NR5R6, OR5, 〇C(=0)R7, C(=〇)〇R5, c(=〇)R5, halogen, 5 or 6 member ring vinegar, C〗-C8 alkyl, 〇 : 2-(:8 dibasic, C2-C8 alkynyl, 201247612 aryl, or glucosyl, wherein 5 or 6 membered ring lactone, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl , aryl, and glucosyl optionally one or more selected from the group consisting of NR5R6, or5, oc(=o)r7, c(=o)or5, c(=o)r5, c]-c8 alkyl, C2 -C8 alkenyl, C2-C8 alkynyl, (3-(:8-cycloalkyl, c,-c8 haloalkyl, and crc8 alkoxy substituents are substituted; each R5, and R6 are each independently Is hydrogen, or c, -c8 alkyl; R7 is Cj-Cg danyl, OR5, or NR5R6; m is 1-12; and η is 1-12. Another embodiment of the present invention provides inhibition A method for expressing NF-κΒ activity and/or transforming growth factor (TGFhpi protein) in a subject, comprising: administering an effective dose of one of cyclohexenone compounds, A pharmaceutically acceptable salt, a metabolite thereof, a solvate thereof, or a prodrug thereof to the host, wherein the cyclohexenone compound has the following structure:

Wherein each X and Y system is independently oxygen, Nr5, or sulfur; R is hydrogen or an alkyl group; each R丨, R2, and R3 are each independently hydrogen, methyl, or (CH2)m -CH3 ; R4 is NR5r6, 〇r5, 〇c(=〇)R7, c(=〇)〇R5, c(=〇)R5, tooth=, 5 or 6 member ring vinegar, C〗 _C8 appearance , C2_c8 dilute group, C2_c8 block group, aryl group, or glucosyl group, wherein 5 or 6 membered ring lactone, C|C8 alkyl group, C2 C8 alkenyl group, C2-Cs alkynyl group, aryl group, and glucosyl group Selective one or more than 8 201247612 is selected from nr5r6, 〇r5, oc(=o)r7, c(=〇)〇R5, c(=0)R5, C|-C8 alkyl, C2-C8 phenyl , C2-C8 block group, c3-C8 ring cyclyl, Ci-C8 dentate group, and C 丨-C8 pit oxygen substituent; each R5, and R6 are independently hydrogen, or CrC8 Alkyl; RACVCs alkyl, OR5, or NR5R6; m is 1 -12; and η is 1-12. Another embodiment of the present invention provides a method of inhibiting ROS/NO and/or p47ph°x of a subject comprising: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof And a metabolite thereof, a solvate thereof, or a pre-drug thereof to the host, wherein the cyclohexenone compound has the following structure:

Wherein each of the X and Y systems is independently oxygen, NR5, or sulfur; the R system is hydrogen, or a CpC^CVCs danic group; each R丨, R2, and R3 are each independently hydrogen, methyl, or ( CH2)m-CH3; R4 is NR5R6, 〇R5, 〇c(=〇)R7, c(=o)or5, c(=o)r5, halogen, 5 or 6 membered ring lactone, CVC8 alkyl, a C2-C8 alkenyl group, a C2-C8 alkynyl group, an aryl group, or a glucosyl group, wherein the 5 or 6 membered ring lactone < Ci-C8 alkyl group, c2-c8 alkenyl group C^C:8 alkynyl group, The aryl group and the glucosyl group are selectively selected from nr5r6, or5, oc(=o)r7, c(=o)or5, c(=o)r5, 201247612 C,-C8, C2 -C8 dilute, (: 2-<:8 alkynyl, c3-C8 cyclodextrin, CVCs haloalkyl, and C|-C8 substituents substituted; each R_5, and R0 are each Independently hydrogen, or Ci_C8; C, -C8 alkyl, 〇r5, or NR5R6; m is 1-12; and η is 1-12. Another embodiment of the present invention provides a reduction of one A method for CD3+/CD69+ sputum cells of a subject, comprising: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, and a solution thereof a compound, or a pre-drug thereof, to the host, wherein the cyclohexenone compound has the following structure:

Wherein each X and oxime is independently oxygen, Nr5, or sulfur; R is hydrogen or CbO^-Ce alkyl; each R丨, R2, and R3 are each independently hydrogen, methyl, or (CH2)m_CH3 ; R4 is NR5R6, 〇R5, 〇c(=〇)r7, c(=〇)〇R5, C(=0)R5, halogen, 5 or 6 member ring vinegar, crC8 alkyl, a c2-C8 dilute group, a C2-C8 alkynyl group, an aryl group, or a glucosyl group, wherein the 5 or 6 membered ring lactone, Ci_C8 alkyl group, C2_C8 alkenyl group, CrC8 alkynyl group, aryl group, and glucosyl group selectivity One or more selected from the group consisting of NR5R6, 0R5, 〇C(=〇)R7, c(=〇)〇R5, c(=〇)R5, C"c8 yard base, c2-c8 base' c2-C8 block Substituting (: 3-(:8-cycloalkyl), CrC8 halo-based, and C|-C8-substituted substituents; 201247612 Each R5, and R0 are each independently hydrogen or Ci_Ce alkyl; I system crci {alkyl, 〇r5, or nr5r6; m is 1-12; and η is 1-12. Another aspect of the present invention provides a glutathione peroxidase that enhances renal magnetic properties ( GPx) methods of activity comprising: administering an effective amount of cyclohexene, a compound, a pharmaceutically acceptable salt thereof, a metabolite, a solvate thereof, or a prodrug thereof to the host, wherein the cyclohexenone compound has the following structure:

Wherein each X and Y system is independently oxygen, nr5, or sulfur; R is hydrogen, or ¢: (=0) (^-(:8 alkyl; each R丨, R2, and R3 are each Independently hydrogen, methyl 'or (CH2)m_CH3; R4 is NR5R6, 〇R5, 〇C(=〇)R7, c(=〇)〇R5, c(=〇)R5, halogen, 5 or 6 members Ring vinegar, leuco, C2-C8+, C2-C8 block, aryl, or glucosyl, wherein 5 or steroidal lactone, CrCs alkyl, C2-C8 alkenyl, CrC8 alkynyl, The aryl group and the glucosyl group are one or more selected from the group consisting of NR5R6, 〇R5, 〇c(=〇)R7, c(=0)0R5, c(=o)r5, yl, C2-C8 , c2-c8 fast radical, c3-c8 cyclodextrin, CVCs halogen-based, and CrCs alkoxy substituents; each 5' and 6-foot each independently argon, or c "C8 alkyl R7 is a C"C8 alkyl group, 〇R5, 4NR5R6; 201247612 m is 1 -12; and η is 1-12. Another embodiment of the present invention provides a method for reducing a proinflammatory cytokine of a subject. Including: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, and a solvate thereof A pharmaceutical or a predecessor to the body, wherein the cyclohexenone compound had the following structure:

Wherein each X and oxime is independently oxygen, NR5' or sulfur; R is hydrogen or CbOA-Cs alkyl; each of Ri, R2, and R3 is independently hydrogen, methyl, or (CH2) m-CH3; R4 is NR5R6, 〇R5, 〇c(=〇)R7, c(=o)or5, C(=0)R5, halogen, 5 or steroidal lactone, crC8 alkyl, C2 -C8 alkenyl, C2-C8 alkynyl, aryl ' or glucosyl' wherein 5 or 6 membered ring lactones, CrC8 alkyl groups, C2-C8 dilute groups, C2_CS alkynyl groups, aryl groups, and glucosyl group selection One or more selected from the group consisting of NR5R6, 〇R5, 〇c(=〇)r7, c(=o)or5, c(=o)r5, CVCV^, C2-C8 alkenyl c2-C8 alkynyl '(: 3-(:8-cycloalkyl, CVC8 comonyl, and Ci-C8 alkoxy substituents are substituted; each R5, and R6 are independently nitrogen or Ci-Cg alkyl; R7 C|-C8 alkyl, 〇r5, or nr5r6; m is 1-12; and η is M2. 12 201247612 Another embodiment of the present invention provides a method for reducing thiocysteine-1 expression in the kidney and / or a method of inhibiting renal NLRP3 activity, comprising: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite, a solvate thereof, or a prodrug thereof to the host, wherein the cyclohexenone compound has the following structure:

Wherein each of the X and Y systems is independently oxygen, NR5, or sulfur; R is hydrogen, or C(=0)C "C8 alkyl; each Ri, R2, and R3 are each independently hydrogen, Indenyl, or (CH2)m-CH3; R4 is NR5R6, OR5, oc(=o)r7, C(=〇)〇R5, c(=〇)R5, element, 5 or 6 membered ring lactone , C--C8 alkyl, c2-c8 alkenyl, C2-C8 block, aryl, or glucosyl' wherein 5 or 6 membered ring lactones, 〇^-(:8 alkyl, C2-C8 晞One or more selected from the group consisting of NR5R6, OR5, 0C(=0)R7, c(=o)or5, c(=o)r5,

Substituted by a substituent of Ci-Cg: C2-C8, C2-C8, C3-C8 cyclohexyl, Cj-C8 haloalkyl, and c"c8 alkoxy; each R5 And 116 are each independently hydrogen or a Crc8 alkyl group; R7 is a Ci-Cg alkyl group, OR5, or NH; m is 1 · 12; and η is 1-12. A further embodiment of the present invention is Provided is a method for reducing the amount of renal NF-κΒ in a kidney comprising: administering an effective dose of one of cyclohexenone compounds 13 201247612, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, or a precursor thereof The drug is applied to the host, wherein the cyclohexenone compound has the following structure:

Wherein each X and Y system is independently oxygen, nr5, or sulfur; R is hydrogen, or (:(=0)<:|-(:8 alkyl; each Ri, R2, and R3 Each is independently hydrogen, sulfhydryl, or (CH2)m-CH3; R4 is NR5R6, 0R5, 〇c(=o)r_7, C(=0)0R5, C(=0)R5, dentate, 5 or 6-membered ring lactone, C!-C8 alkyl group, C2-C8 dilute group, c2-c8 fast group, aryl group, or glucosyl group] wherein 5 or 6 membered ring lactone, C, -C8 alkyl group, C2 -C8 dilute, CrC8 alkynyl, aryl, and glucosyl selective one or more selected from nr5r6, or5, 〇c(=o)r7, c(=o)or5, c(=o)r5 Substituting for a substituent of a Ci-Cs, a c2-c8 dilute group, a c2-c8 fast group, a c3-c8 cyclodyl group, a Ci-Ce adentate group, and a C丨-C8 alkoxy group; each Rs And Re are each independently hydrogen or a Ci-Cs alkyl group; R7 is a cvc8 alkyl group, or5, or NR5R6; m is 1-12; and π is 1 -12. Yet another embodiment of the present invention is Provided is a method for inhibiting apoptosis in a kidney, comprising: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, or a precursor thereof 4 201247612 Drugs to the host, wherein the cyclohexenone compound has the following structure:

Wherein each X and Y system is independently oxygen, NR5, or sulfur; R is hydrogen, or C (=〇)Cl-C8 alkyl; each R, r2, and r3 are each independently hydrogen , fluorenyl, or (CH2)m_CH3; R4 is NR5R6, or5, oc(=o)r7, c(=o)or5, c(=o)r5, halogen, 5 or 6 membered ring lactone, C, -C8 alkyl, c2-c8 alkenyl, C2-C8 alkynyl, aryl, or glucosyl, wherein '5 or 6 membered ring lactone, CrC8 alkyl, C2-C8 dilute, CrC8 alkynyl, aryl And one or more selected from the group consisting of nr5r6, OR5, 0C(=0)R7, c(=o)or5, c(=o)r5, CrC8, and (:2-0:8) Substituted by a substituent of a dilute group, a c2-c8 fast group, a C3-C83t alkyl group, a CVC8 i alkyl group, and a CrCs alkoxy group; each of the Rs and R6 groups is independently hydrogen or a C^-Cs alkyl group R7 is Crc8 alkyl, or5, or nr5r6; m is 1-12: and η is 1-12. Another embodiment of the present invention provides protection or prevention of renal sclerosing in a subject kidney / or method of glomerulonephritis, comprising: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, Metabolite, solvate 'or the precursor of the drug to the body, in order to reduce the kidney 15201247612 TGHM protein and levels of expression of protein _ Shu, eye ιν protein aggregation' where 'the cyclohexenone compound had the following structure:

Wherein each of the X and Y systems is independently oxygen, NR5, or sulfur; R is hydrogen, or CpC^CVCs alkyl; each R, R2, and R3 are each independently hydrogen, methyl, or ( CH2)m CH3 ; R4 is NR5R6, OR5, 〇C(=〇)R7, c(=〇)OR5, c 〇)r5, halogen, 5 or 6 member ring vinegar, CVCs alkyl, (: 2 -0:8 dilute, c2-c8 alkynyl, aryl, or glucosyl, wherein 5 or 6 membered ring lactone, Cl_C8 alkyl, C2_C8 alkenyl, C2_C:8 alkynyl, aryl, and glucosyl Selectively one or more selected from the group consisting of NR5R6, OR5, 〇c(=〇)r7, c(=〇)〇R5, c(=〇)R5, c]-c8 alkyl, c2-c8 alkenyl' Substituting a c2-c8 block group, a C3_C8 cycloalkyl group, a C|_Cg haloalkyl group, and a substituent of a Ci-Cg alkoxy group; each Rs, and each of the groups is independently hydrogen or a C|-C8 alkyl group; R7 is a Ci-Cg alkyl group, OR5, or NR5R6; m is 1-12; and η is 1-12. A further aspect of the present invention provides a method for treating a subject with localized squamous sclerosis ( The method of FSGS) comprises: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, and metabolism thereof a solvate thereof, or a pre-drug thereof, to (i) increase Nrf2 activity in the kidney and/or (ii) inhibit NF-κΒ-related inflammatory response in the kidney and 201247612 TGF-βΙ-induced fibrosis, wherein The cyclohexenone compound has the following structure:

Wherein 'each X and Y are each independently oxygen, NR5, or sulfur; R is hydrogen, or CpCOCVCe alkyl; each R!, R2, and R3 are each independently hydrogen, methyl, or (CH2) m_CH3 ; R4 is NEL5R6, or5, oc(=o)r7, c(=o)or5, C(=〇)R5, halogen, 5 or 6 membered ring lactone, CVCe alkyl, c2-c8 alkenyl, a c2-c8 alkynyl, aryl, or glucosyl group, wherein 5 or 6 membered ring lactones, CrCs alkyl groups, c2-C8 dilute groups, Cr-C8 alkynyl groups, aryl groups, and glucosyl group selectivity One or more selected from nr5r6, OR5, 〇C(=〇)R7, C(=0)OR5, c(=〇)r5, CrC8 alkyl, (:2-(:8 dilute, C2-C8) Substituted by alkynyl, C3-C8 cycloalkyl, CVCs dentate, and C丨-C8 alkoxy substituents; each R·5, and R·6 are each independently hydrogen or c丨-c8 An alkyl group; R? is a cvc8 alkyl group, 〇r5, or nr5r6; m is 1 -12 and η is 1-12. A further aspect of the present invention provides a method for treating a subject of renal glomerulonephritis The method comprises: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, Or a pre-existing drug to the host to inhibit the activation of renal NLRp3 inflammatory body and 17 201247612 / or (11) to inhibit the increase of T cell activity, wherein the cyclohexenone compound has the following structure:

Wherein 'each X and γ are each independently oxygen, NR5, or sulfur; R is hydrogen, or CpcOCi-Cg alkyl; each Ri, R2, and r3 are independently argon, sulfhydryl, or (CH2) m_CH3; R4 is NhR6, or5, oc(=o)r7 'c(=o)or5, c(=o)r5, halogen, 5 or 6 member ring vinegar, c丨·c8 alkyl, c2_c8 a C2_C8 alkynyl, aryl, or glucosyl group, wherein '5 or 6 membered ring lactone, Ci-Cs alkyl, C2-C8 dilute, CyC:8 alkynyl, aryl, and glucosyl selective One or more selected from nr5r6, or5, 〇c(=o)r7, c(=o)or5, c(=o)r5, Ci-C8 alkyl, c2-C8 dilute, C2-C8 alkynyl , C3-C8 cyclodextrin, "substituent, Ci-Cs i dyl, and crc8 alkoxy substituents; each and each of the cores are independently hydrogen, or C丨_C8 alkyl; R_7 is Ci- C8 alkyl, hydrazine R5, or nr5r6; m is 1-12; and η is 1-12. A further aspect of the present invention provides a method for slowing down a subject of immunoglobulin-type glomerulonephritis (IgAN), comprising: administering an effective dose of one of cyclohexenone compounds, which is pharmaceutically acceptable Accepting a salt, a metabolite thereof, a solvate thereof, or a pre-drug thereof to the subject, (提升) enhancing Nrf2 18 201247612 activity and/or (ii) inhibiting NF-κΒ-related inflammatory response and TGF-βΙ in the kidney Induced fibrosis 'where' the cyclohexenone compound has the following structure:

Wherein each of X and Y is independently oxygen, NR5, or sulfur; R is hydrogen or CpOK^-Cs alkyl; each R,, R2, and R3 are independently hydrogen, sulfhydryl, Or (CH2)m_CH3; R4 is NR5R6 ' or5, oc(=o)r7, c(=o)or5, C(=0)R5, halogen, 5 or 6 membered ring lactone, (VC8 alkyl, c2 a -c8 alkenyl group, a c2-c8 fast group, an aryl group, or a glucosyl group, wherein '5 or 6 membered ring lactones, C "C8 alkyl group, c2-C8 dilute group, C2-C8 fast group, aryl group, and One or more selected from the group consisting of NR5R6, OR5, 0C(=0)R7, C(=0)〇R5, (^=〇)r5, phenyl, C2-C8 alkenyl, C2-C8 Substituted by a substituent of a c3-c8 ring group, a Ci-Cs haloalkyl group, and a C丨-C8 alkoxy group; each Rs and 116 groups are each independently hydrogen or a C,-C8 alkyl group; R7 is C|-C8 alkyl, OR5, or NR5R6; m is 1-12; and η is 1 -12. All the documents, patents, and patents mentioned in the present invention are incorporated in the contents of the present invention. For reference, that is, the various documents, patents, or patents that are expressly incorporated herein by reference in their entirety are hereby incorporated by reference. 201247612 Kidney spheroid disease includes many diseases caused by a variety of genes and environmental factors, but it is mainly divided into two categories: glomerulosclerosis and glomerulonephritis. Kidney sclerosing, especially FSGS, should be mainly The spheroidal epithelial cells are responsible for the complex reactions in the glomerulus. These complex reactions can include oxidative stress, inflammatory responses to macrophage aggregation, and factors that promote matrix production and/or matrix breakdown. Activation of systemic T cells and lymphocytic/macrophage/neutrophil infiltration, easily lead to the accelerated development of immunoglobulin A (IgAN), which is a common source of glomerulonephritis. However, The prevention and treatment of the degree of aggregation and deterioration of IgAN has not been extensively studied. Here, the present invention provides a method for treating kidney disease, particularly a method for treating glomerulosclerosis or glomerulonephritis, which is The cyclohexenone compound provided by the present invention is administered to a host (e.g., 'human). The cyclohexenone compound has a subject (especially a kidney) The therapeutic effect can be used to treat renal sclerosing (as shown in Examples 16, 14) and/or glomerulonephritis (as shown in Examples 7-13, 14). A method for treating a kidney disease of a main vessel, such as glomerulosclerosis or glomerulonephritis. The method comprises: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, and a metabolite thereof And a solvate thereof, or a pre-drug thereof, to the host, wherein the cyclohexenone compound has the following structure: Λ

Wherein 'each X and oxime are each independently oxygen, NR5, or sulfur; 20 201247612 R is hydrogen, or <:(=0)(^-(:8 alkyl; each R, R2, and R3 is independently hydrogen, methyl or (CH2)m-CH3; R4 is NR5R6, OR5, 〇C(=〇)R7, C(=0)0R5, c(=o)r5, halogen, 5 Or 6-membered ring lactone, CrC8 alkyl, c2-C8 alkenyl, c2-c8 alkynyl, aryl, or glucosyl, wherein '5 or 6 membered ring lactone, CrC8 alkyl, C2-C8 alkenyl, The CrC8 alkynyl, aryl, and glucosyl group are selected from one or more selected from the group consisting of NR5R6, OR5, OC(=〇)R7, C(=0)0R5, c(=o)r5, CrCs alkyl, c2 Substituted by a substituent of -c8 alkenyl, c2-c8 alkynyl, C3-C8 cycloalkyl, c丨-c8 haloalkyl, and C丨-C8 alkoxy; each Rs, and R6 are independently Hydrogen, or (: 丨-(:8 alkyl; R7-based Ci-Cg alkyl, OR5, or NR5R6; m is 1-12; and η is 1-12 〇 in some embodiments, provides a therapeutic kidney A method of spheroid sclerosis. In a specific embodiment, the glomerulosclerosis is local glomerulosclerosis (FSGS) or nodular glomerulosclerosis. In the case of glomerulosclerosis, local glomerulosclerosis (FSGS) is used. In some embodiments, the cyclohexenone compound prevents oxidative stress. In a particular embodiment, the TGF-β Ι cell is reduced by transmission. The outer matrix protein is expressed to prevent oxidative stress. In some embodiments, the primary system is human. In a specific embodiment, the oxidative stress is reduced by increasing the renal factor _E2 correlation factor 2 (Nrf2) activity. In some embodiments, 'providing a method for treating glomerulonephritis', in a specific embodiment, the glomerulonephritis is an immunoglobulin type 8 kidney filament 201247612 glomerulonephritis (IgAN). In some embodiments, The enone compound reduces CD3+/CD69+ T cells in the subject. In a particular embodiment, the cyclohexenone compound reduces proinflammatory cytokines in the subject. In a particular embodiment, the proinflammatory cytokines include MCP-1, IL- 6. IL-Ιβ, IL-18, or a combination thereof. In some embodiments, the primary system is a human. In some embodiments,

The cyclohexanone compound of the structure can be prepared synthetically or semi-synthetically from any suitable starting material. In other embodiments, the cyclohexenone compound can be prepared by fermentation, or other similar methods. For example, in some cases, compound 1 (known as Antroquinonol® or "Antroq"), or compound 3 may be derived from 4-hydroxy-2,3-dimethoxy-6-methyl ring Prepared by 4-hydroxy-2,3-dimethoxy-6-methylcyclohexa-2,5-dienone. Non-limiting examples of the compounds are shown below. ch3 ch3 ch3 ch3

0, 1 ch3 ch3 ch3 ch3 ch3

22 201247612

23 201247612

OH

CH, CH-, CH, CH,

The cyclohexenone compound of the structure is an organic solvent extract of Antrodia camphorata. In some embodiments 24 201247612, the organic solvent is selected from the group consisting of alcohols (eg, methanol, ethanol, propanol, or bean analogs), vinegar members (eg, 'methyl acetate, ethyl acetate, or the like) , burning (such as 'Eight Court, burned, Gengyuan, or similar things), _ (eg, methyl chloride, gas, sputum, gas, two gas, or similar), and bean phase = Things. For example, the exemplary compound N7 can be isolated from an organic solvent extract. In a particular embodiment, the organic solvent is an alcohol; and in a particular embodiment, the alcohol is ethanol. In some embodiments, the cycloheximide compound is isolated from an aqueous extract of Antrodia camphorata. In some embodiments, the method of the invention for alleviating renal dysfunction or glomerular damage comprises: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, and a solvent thereof. a compound, or a pre-drug thereof, to a host, wherein the cyclohexenone compound has the following structure:

Wherein 'each X and Y are each independently oxygen, NR5, or sulfur; R is hydrogen, or c〇=o) crc8 alkyl; each of Ri, R2, and R3 is independently hydrogen, methyl, Or (CH2)m_CH3; R4 is NR5R6, 〇R5 ' 〇c(=〇)R7, c(=o)or5, c(=o)r5, halogen, 5 or 6 membered ring lactone, CrCs alkyl' C2-c8 alkenyl, C2-C8 alkynyl, aryl, or glucosyl' wherein 5 or 6 membered ring lactone, Ci-Cs alkyl, c2-c8 dilute, Ci-Cg alkynyl, aryl, And one or more selected from the group consisting of NR5R6, 〇R5, 〇c(=〇)R7, c(=o)or5, c(=o)r5, 25 201247612 C,-C8:^, C2_C8 dilute group, C2_C8 fast group, C3_C4 alkyl group, C|_C8 dentate group, and c"c8 alkyl fluorenyl substituent; each R5, and R0 are independently argon or crc8 alkyl; R7 C, -C8 alkyl, 〇r5, or Nr5r6; m is 1 -12; and η is 1-12. In some embodiments, renal glomerular damage includes epithelial hyperplasia (EPHL), in some embodiments The main system is human. In some embodiments, the cyclohexenone compound provided by the present invention has an increase in renal cell nuclear factor. _Ε2 correlation factor 2 (Nrf2) activity, but inhibits the NF-κΒ-related inflammatory response in the renal pelvis and the therapeutic efficacy of the TGF-βΙ-induced fibrotic pathway. See Examples 5, 6 and 14. Partial implementation of the present invention A method for increasing the renal cell nuclear factor-E2 correlation factor 2 (Nrf2) activity of a subject comprises administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, and a solvate, or a prodrug thereof, to the main compound, wherein the cyclohexenone compound has the following structure:

Wherein 'each X and γ are each independently oxygen, Nr5, or sulfur; R is hydrogen, or C(=0)C, -C8 alkyl; each R〇, R2, and R3 are each independently hydrogen , methyl, or (CH2)m_CH3 ; 26 201247612 R4 is NR5R6, OR5, 〇c(=〇)r7, C(=〇)〇R5, C(=0)R5, halogen, 5 or 6 member ring Vinegar, CrC8 leucoyl, c2-C8 alkenyl, C2-C8 fast radical, aryl, or glucosyl' wherein 5 or 6 membered cyclic lactones, C"C8 alkyl, C2-C8 alkenyl, CrC8 alkynyl , one or more selected from the group consisting of NR5R6, 〇R5' 〇c(=〇)r7, C(=0)0R5, C(=0)R5, yl, c2-c8 Substituent, C2-C8 fast radical, C3-C8 cyclosporin "substituent, CVCs dentate, and C" C8 methoxyl substituent; each Rs, and R6 are each independently hydrogen, or C1_C8 alkyl ;

RySCVCs alkyl, hydrazine R5, or NR5R6; m is 1-12; and η is 1-12. In some embodiments, the primary system is a human. Some embodiments of the present invention provide a method of inhibiting renal NF-kB activity and/or transforming growth factor protein expression of a host, comprising: administering an effective dose of one of a cyclohexenone compound, which is pharmaceutically acceptable a salt, a metabolite thereof, a solvate thereof, or a prodrug thereof to a host, wherein the cyclohexenone compound has the following structure:

Wherein each X and Y system is independently oxygen, Nr5, or sulfur; R is hydrogen, or C(=〇)C, -C8 alkyl;

Each R|, R2, and R3 is independently hydrogen, methyl' or (CH2)m_CH 27 201247612 R4 is NR5R6, OR5, oc(=o)r7, c(=o)or5, c(=o) R5, halogen, 5 or 6 membered ring lactone, Ci-Cs alkyl, C2-C8 alkenyl, c2-c8 alkynyl, aryl, or glucosyl' wherein 5 or 6 membered vinegar, Ci-Cg One or more selected from the group consisting of NR5R6, 〇R5, 0C(=0)R7, C(=0)0R5, thiol, C2-C8 alkenyl, C2-C8 alkynyl, aryl, and glucosyl. Substituted by a substituent of C(=0)R5, Ci-Cg alkyl, C2.Cs, Cz-Cg, C3-C8 cycloalkyl, Ci-Cg haloalkyl, and crc8 alkoxy; Each of R5 and R6 is independently argon or C,-C8 alkyl; R7 is C|-C8 alkyl, OR5, or NR5R6; m is 1-12; and η is 1-12. In some embodiments, the primary system is a human. In some embodiments, administration of the cyclohexenone compound (eg, Compound 1) provided by the present invention inhibits the production of r〇s/n〇 and p47ph〇x NAD(P)H oxidase in the kidney, but Significantly increase the Nrf2 signaling pathway associated with the action of cyclohexenone compounds on FSGS. See Examples 3, 5, and 14. Some embodiments of the present invention provide a method of inhibiting ROS/NO and/or p47~ of a subject, comprising: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, and a metabolite thereof And a solvate thereof, or a prodrug thereof, to the host, wherein the cyclohexene oxime compound has the following structure: 28 201247612

Wherein 'each X and Y are each independently oxygen, NR5, or sulfur; R is hydrogen, or (:(=0)0^-(:8 alkyl; each R!, R2, and R3 are each Independently hydrogen, methyl, or (CH2)m_CH3; R4 is NR5R6, OR5, OC(=〇)R7, c(=〇)〇r5, c(=0)R5, halogen, 5 or 6 membered ring Vinegar, Cl-C8 alkyl, c2_C8 dilute, C2_c8 alkynyl, aryl, or glucosyl, wherein 5 or 6 membered ring lactone, CrC8 alkyl, C2-C8 alkenyl, Cz-C:8 alkynyl One or more selected from the group consisting of NR5R6, OR5, 〇C(=〇)r7, c(=〇)〇R5, c(=o)r5, • base, C2-C8 Alkenyl, c2-c8 alkynyl, c3-C8 cyclohexanyl, c,-c8 halo, and Ci-Cs alkoxy substituents; each R5, and R6 are independently hydrogen, Or Cl_c8 alkyl; R>7 is C!-Cg alkyl, OR5, or NR5R6; m is 1-12; and η is 1-12. In some embodiments, the main system is human. The invention provides a method for reducing a CD3+/CD69+ Τ cell of a main Zhao, comprising: administering an effective dose of one cyclohexenone compound, which is pharmaceutically acceptable Salts, their metabolites, solvates thereof, pharmaceutical or a predecessor to the body, wherein the cyclohexenone-based compound having the following structure: 29 201 247 612

Wherein each X and γ system is independently oxygen, Nr5, or sulfur; R is hydrogen, or ¢: (=0) (:, - (: 8 alkyl; each R丨, R2, and R3 Each is independently hydrogen, methyl, or (CH2)m_CH3; R4 is NR5R6, 〇R5, 〇c(=〇)r7, c(=〇)OR5, cdi)r5, halogen, 5 or 6 membered ring Lactone, C|-C8 alkyl, c2-C8 dilute, C2-C8 alkynyl, aryl, or glucosyl, wherein 5 or 6 membered ring lactone, Ci_c8 alkyl, c2_C8 alkenyl, alkynyl, The aryl group and the glucose group are selectively selected from one or more selected from the group consisting of NR5R6, 〇R5, 〇C(=〇)R7, c(=0)OR5, c(=o)r5, C"c8, and c2 Substituted by -c8 dilute, c2-c8 block, C3-C8 cycloalkyl, CrCs haloalkyl, and CrC8 alkoxy; each Rs, and 116 are independently hydrogen, or G-Cs alkyl;

RtSQ-Cs alkane, 〇R5, or NR5R6; m is 卜12; and η is 1-12. In some embodiments, the primary system is a human. It has been found that FSGS mice exhibit a significant increase in GPx activity after 7 days of disease induction (as shown in Examples 4 and 14). Oxidative stress and its associated inflammatory response are common features of chronic kidney disease (Kim, et al., j/w J Physiol Renal Physiol, 298: F662-671, 2010; Yoon, et al., /«i, 71: 167-172, 2007), and plays an important role in the development of renal sclerosing. It is important to note that 'oxidative stress and inflammatory response 30 201247612 are closely related to each other, and either one induces and amplifies the other, causing a vicious circle. For example, oxidative stress can include activation of NF-κΒ, and the associated inflammatory factors and chemotactic reactions caused by Chemokine, resulting in leukocyte activation and ROS/NO production and release, which in the kidneys Oxidative pressure (Anrather, et al., Price / Chem, 281: 5657-5667, 2006; Vaziri, et al., Nat Clin Pract Nephrol, 2: 582-593, 2006; Rodrigo, et al., Free Radio Biol Me 33: 409-422, 2002). In addition, compared with normal mice, NF-kB activation and its subsequent initiation of type 2 epoxidase, induced nitric oxide synthase, L-6, and TNF-α cause Nrf2 gene defects. Severe inflammatory response in mice (Chen, et al., J/w «/ //eari CZrc 290: HI862-1870, 2006; Li, et al., Biochem Pharmacol, 76: 1485-1489, 2008). In addition, studies have shown that HO-1 deficiency can also cause glomerular sclerosis, in which HO-1 is regulated by Nrf2 (Datta, et al., J dw Soc from ?/7/2 〇 /, 10: 2540-2550, 1999). In some embodiments, administration of a cyclohexenone compound (e.g., Compound 1) provided by the present invention significantly reduces renal IL-6 expression and inhibits NF-κΒ activation in the kidney. As a result of FSGS+Antroq mouse experiments, it has been confirmed that T cells and macrophages infiltrate into the kidney and can be significantly inhibited (see Examples 5, 11 and 14). In some embodiments, the mechanism of action is related to the inhibition of interstitial inflammation and EPHL, among which EPHL is one of the major factors contributing to the development of FSGS in the kidney (D'Agati, V Sewi/i 23: 1 17-134). , 2003; Nagata, et al., Lab Invest, 80: 869-880, 2000) 〇y y201247612 Some embodiments of the invention provide a method of increasing glutathione peroxidase (GPx) activity in the kidney, including : administering an effective amount of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof or a prodrug thereof to the host, wherein the cyclohexenone compound has the following structure:

Wherein 'each X and Y are each independently oxygen, NR5, or sulfur; R is hydrogen, or C(=0)C"C8 alkyl; each R, R2, and R3 are each independently hydrogen, Methyl or (CH2)m-CH3; R4 is NR5R6, 〇r5, 〇c(=〇)r7, c(=0)0R5, C(=0)R5, halogen, 5 or 6 membered ring lactone , CrCe alkyl, C2-C8 alkenyl, C2-C8 alkynyl, aryl, or glucosyl, wherein 5 or 6 membered ring lactone, Ci-Cs, C2_C8, C2-C8, The aryl group and the glucosyl group are selected from one or more selected from the group consisting of NR5R6, 〇r5, 〇c(=〇)r7, c(=0)〇R5, c(=o)r5, CVCs alkyl, C2- Substituted by a C8 alkenyl group, a c2-C8 alkynyl group, a c3-c8 cycloalkyl group, a c!-c8 haloalkyl group, and a substituent of a Ci-Cs alkoxy group; each Rs and R0 are each independently hydrogen' Or C丨·c8 alkyl; R7 is a Ci-Cg alkyl group, or5, or nr5r6; m is 1 -12; and η is 1-12. In some embodiments, the 'main system is human. 32 201247612 Some embodiments provide a method for reducing a pro-inflammatory cytokine of a subject 'including: administration-effective dose of one cyclohexenone compound', pharmaceutically acceptable The salts, their metabolites, solvates' or its predecessors to the main medicament n, wherein the Si compound is cyclohexene column having the structure:

Wherein each of the X and γ systems is independently oxygen, NR5, or sulfur; R is hydrogen or CPOKVCs; each R丨, R2, and R3 are independently hydrogen, methyl, or (CH2) m_CH3; R4 is NR5R6, 〇R5, 〇C(=〇)R7, C(=〇)〇R5, c(=〇)r5, halogen, 5 or 6 member ring vinegar, C!-C8 yard, a c2-C8 dilute group, a C2-C8 block group, an aryl group, or a glucosyl group, wherein 5 or a member of the ring lactone, an alkyl group, a C2-C8 alkenyl group, a CrC8 alkynyl group, an aryl group, and a glucosyl group are selected One or more selected from the group consisting of NR5R6, OR5, 〇C(=〇)R7, C(=0)0R5, C(=0)R5, CVCs, C2-C8 dilute, c2-c8 fast radical, Substituted by a substituent of a c3-c8 cycloalkyl group, a C-C8 haloalkyl group, and a CrCs alkoxy group; each R5 and R6 are each independently hydrogen or a Crc8 alkyl group; RACi-Ce alkyl, fluorene R5, or NR5R6; m is 1-12::: and η is 1-12 » In some embodiments, the 'main system is human. 33 201247612 A portion of the present invention provides a method of reducing thiocysteine-1 expression in the kidney and/or inhibiting renal NLRP3 activity, comprising: administering an effective dose of one of the cyclohexenone compounds, which is pharmaceutically acceptable Accepting a salt, a metabolite thereof, a solvate thereof, or a prodrug thereof to the host, wherein the cyclohexenone compound has the following structure:

Wherein each of the X and Y systems is independently oxygen, NR5, or hydrazine; R is hydrogen or an alkyl group; each of R, R2, and R3 is independently hydrogen, methyl, or (CH2)m -CH3 ; R4 is nr5r6, or5, oc(=o)r7, c(=o)or5, c(=o)r5, halogen, 5 or 6 membered ring lactone 'Ci-Cs alkyl, C2-C8 Alkenyl, C2-C8 alkynyl, aryl, or glucosyl, wherein 5 or 6 membered ring lactone, C^-Cs alkyl, C2-C8 alkenyl, C^Cg alkynyl 'aryl, and glucose One or more selected from the group consisting of NR5R6, or5, oc(=o)r7, c(=o)or5, c(=o)r5, c]-c8 alkyl, C2-C8 alkenyl, C2 Substituted by a substituent of -C8 alkynyl, C3-C8 cycloalkyl, CVCs haloalkyl, and CrCs alkoxy; each r5, and 6 is independently nitrogen, or c,-c8 alkyl; ISCVCe Alkyl, OR5, or NR5R6; m is 1-12; and η is 1-12. In some embodiments, the primary system is a human. 34 201247612 A method of activity comprising: administering a pharmaceutically acceptable salt thereof; and stimulating a drug to the subject, wherein: the present invention provides a method for reducing renal-effective dose in the kidney a cyclohexenone compound, a substitute thereof, a solvate thereof, or a pre-cyclohexanthene compound thereof having the following

Wherein 'each X and oxime are each independently oxygen, Nr5, or sulfur; R is hydrogen '* or CpCOCnCe alkyl; each R丨, R2, and R3 are each independently hydrogen, methyl, or R4 Is NR5R6, OR5, 〇C(=0)R7, c(=〇)〇R5 'c(=0)R5, halogen, 5 or 6 membered vinegar, Ci-C8^, c2-C8 alkenyl, a c2-c8 alkynyl, aryl, or glucosyl group wherein 5 or 6 membered cyclo lactone, Cl-C8 alkyl, c2_C8 alkenyl, Cr-Cs alkynyl, aryl, and glucosyl-selective One or more selected from the group consisting of NR5R>6, 0R5, 〇C(=〇)R7, c(=〇)〇R5, C(=0)R5, CVCs alkyl, C2-C8 dilute, c2-c8 alkynyl' Substituted by a substituent of the c3-C8 ring-based group 'CKC8 haloalkyl, and c丨-C8 alkoxy; each R5, and Re are each independently hydrogen or C|-C8 alkyl;

RjCi-C; alkyl, hydrazine R5, or NR5R6; m is 1-12; and η is 1-12. In some embodiments the 'main system is human. 35 201247612 A portion of the present invention provides a method for inhibiting cell death in the kidney comprising: administering an effective dose of one of the cyclohexenone compounds, a pharmaceutically acceptable salt thereof, a metabolite thereof, and a solvate thereof. Or a pre-drug thereof to the host, wherein the cyclohexenone compound has the following structure:

Wherein each 'X and γ are each independently oxygen, nr5, or sulfur; R is hydrogen or an alkyl group; each R丨, R2, and R3 are each independently hydrogen, methyl, or (CH2)m_CH3 R4 is NR5R6, 〇R5, 〇c(=〇)r7, c(=〇)〇R5, C(=〇)R5, halogen, 5 or 6 member ring vinegar, Cl_c8 炫, C2_C8 rare group, C2_C8 alkynyl, aryl, or glucosyl, wherein 5 or 6 membered ring lactone, Ci_C8 alkyl, C2_C8 alkenyl, C^-C:8 alkynyl, aryl, and glucosyl selective Or above selected from nr5r6, 〇r5, 〇c(=〇)r7, c(=o)〇r5, c(=o)r5, cvc8 alkyl, (: 2-(:8 dibasic, c2-c8 fast Substituted by a substituent of a c3-c8 cycloalkyl group, (a VC8-complex group, and a Ci-Cs alkoxy group; each R5, and Re is independently hydrogen or a Ci-C8 alkyl group; 〇R5, or NR5R6; m is 1-12; and η is 1-12. In some embodiments, the primary system is human. Some embodiments of the present invention provide protection or prevention of renal spheroid sclerosis in a subject kidney And/or renal interstitial fibrosis and/or renal glomerulonephritis 36 201247612, including: An effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, or a prodrug thereof to the subject to reduce the expression of TGF_P 1 protein in the kidney and collagen I, III, and IV protein aggregation ' Among them, the cyclohexenone compound has the following structure:

Wherein 'each X and Y are each independently oxygen 'NR5, or sulfur; R is hydrogen or C(=0)C|-C8 炫; each Ri, R2, and R_3 are independently hydrogen' Methyl, or (CH2)m_CH3; R4 is NR5R6, OR5, 〇C(=〇)R7, c(=o)or5, c(=o)r5, halogen, 5 or 6 member vinegar, CVCs a c2-c8 alkenyl group, a C2-C8 alkynyl group, an aryl group, or a glucosyl group, wherein '5 or 6 membered ring lactones, alkyl groups, C2-C8 alkenyl groups, CrC8 alkynyl groups, aryl groups, and glucosyl groups Selectively one or more selected from the group consisting of NR5R6, or5, 〇c(=o)r7, c(=o)or5, c(=o)r5,

Substituted by a substituent of a CkCs alkyl group, a C2-C8 alkenyl group, a C2-C8 alkynyl group, a c3-c8 cycloalkyl group, a Ci-Cs haloalkyl group, and a Ci-Ce alkoxy group; each R5, and 116 series Each is independently hydrogen or a Ci-Cs alkyl group; alkyl, hydrazine R5, or NR5R6; m is 1-12; and η is M2. In some embodiments, the primary system is a human. 37 201247612 Oxidative stress caused by increased production of reactive oxygen species (ROS) and/or nitric oxide (NO) and impaired antioxidant capacity, may lead to necrosis, apoptosis, inflammation, fibrosis and other kidney diseases (See Kim, et al., dm J_P/j less. π·ο/ corpse/2>^〇/, 298: F662-671, 2010). In recent years, studies on the skein section/hardening mechanism of kidney have found that the NAD(P)H oxidase enzyme complex of infiltrating white blood cells in kidney injury and kidney cells itself is highly correlated with superoxide production (IBID; Jones, Et al., J dm Soc Nephrol, 5: 1483-1491, 1995; Radeke, et al., J Biol Chem, 266: 21025-21029, 1991). Inhibition of oxidative stress improves kidney hardening through anti-inflammatory and anti-apoptotic processes. In addition, the nuclear factor-E2 correlation factor 2 (Nrf2) is a transcription factor that, in a variety of cells and tissues, is associated with antioxidant responses in the promoter region of genes that encode multiple antioxidant and second-phase enzymes. Factor binding, such as glutathione peroxidase (GPx), catalase, and superoxide dismutase (Itoh, et al) Biochem Biophys Res Commun, 236: 313-322, 1997; Nguyen, et al., CTzew, 284: 13291-13295, 2009). Nrf2-related regulation of cellular antioxidant responses and anti-inflammatory mechanisms is closely related to antioxidant stress; whereas in mouse renal tubular epithelial cells, Nrf2 signaling Pathways are associated with renal spheroid protection through transforming growth factor (TGF)-pi-related epithelial-mesenchymal transition (Shin, et al., Free 5ι·ο/ Mei/, 48: 1051-1063, 2010), and at the same time associated with streptozotocin-induced diabetic nephropathy (Jiang, et al, 59: 850-860, 2010), the performance of sputum fibrosis-associated cytokines, especially TGF-β 1, High with renal hardening/fibrosis Degree correlation (Ka, et al., «/ dm Soc TVep/iro/, 18: 38 201247612 1777-1788, 2007; Lan, HY. Front Biosci, 13: 4984-4992, 2008; Zhao, et al·, d /w «/TVep/iz-o/, 28: 548-554, 2008). It has been confirmed that by reducing the expression of TGF-βΙ and extracellular matrix proteins, inhibition of oxidative stress can be achieved, thereby improving spheroid atherosclerosis. (Hahn, et al., corpus ecfiair Nephrol, 13: 195-198, 1999; Kashihara, et al., Curr Med C/zem.; Manning, et al., dw «/25: 3 11-3 17,2005 In addition, in mouse renal tubular epithelial cells and streptozotocin-induced diabetic nephropathy, the anti-oxidative stress message associated with Nrf2 transcription factor and its second phase enzyme protects renal fibrosis. For example, when a cyclohexenone compound (such as Compound 1) provided by the present invention is administered, the amount of TGF-βΙ protein in the kidney and the aggregation of collagen I, III and IV downstream thereof can be reduced (see Examples 6 and 14); this result represents that the cyclohexenone compound provided by the present invention is permeable to inhibit TGF-βΙ-related fibrosis in FSGS-treated mice. Diameter 'of protection in kidney glomerular sclerosis and interstitial fibrosis. Some embodiments of the present invention provide a method of treating localized renal sclerosing sclerosis (FSGS) in a subject comprising: administering an effective amount of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite, a solvate thereof, or a pre-drug thereof to the host, (i) increasing Nrf2 activity and/or (Π) inhibiting NF-κΒ-related inflammatory response in the kidney and TGF-βΙ-induced fibrosis, wherein The cyclohexanone compound has the following structure.

201247612 wherein each of the ruthenium and Y is independently oxygen, NR5, or sulfur; R is hydrogen, or CpOKrCs alkyl; each R, R2, and R3 are each independently ammonia, methyl, or (CH2) m-CH3; R4 is NR5R6, OR5, oc(=o)r7, c(=o)or5, c(=o)r5, halogen, 5 or 6 membered ring lactone, CVC8 alkyl, C2-C8 Alkenyl, C2-C8 alkynyl, aryl, or glucosyl, wherein 5 or 6 membered ring lactone, CrC8 alkyl, C2-Cs alkenyl, C2-C8 alkynyl, aryl, and glucosyl group are selected One or more selected from NR5R6, or5, oc(=o)r7, c(=o)or5, c(=o)r5, CrC8 alkyl, C2-C8 alkenyl, c2-c8 alkynyl, C3 Substituted by a C8 cycloalkyl, C,-C8 haloalkyl, and crc8 alkoxy substituent; each R5, and 116 are each independently hydrogen or C丨-c8 alkyl; ISCi-Ce alkyl , 〇R5, or NR5R6; m is 1-12; and η is 1 -12. In some embodiments, the primary system is a human. Some embodiments of the present invention provide a method of treating renal glomerulonephritis in a subject comprising: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, and a solvate thereof. Or a pre-drug to the subject, (i) inhibiting activation of renal NLRP3 inflammatory body and/or (ii) inhibiting an increase in T cell activity, wherein the cyclohexenone compound has the following structure:

40 201247612 wherein 'each X and Y are each independently oxygen, nr5, or sulfur; R is hydrogen, or CpOKVCs alkyl; each R, R2, and R3 are each independently hydrogen, methyl, or (CH2)m_CH3 ; R4 is NR5R6, OR5, 〇C(=〇)R7, c(=〇)〇R5, C(=0)R5, _素, 5 or 6 members of the ring vinegar, 0 "< :8 alkyl, c2-C8 dilute, C2-C8 alkynyl, aryl, or glucosyl' wherein 5 or 6 membered cyclic lactones, (^-<:8 alkyl, C2-C8 alkenyl, The CrC8 alkynyl, aryl, and glucosyl group are selected from one or more selected from the group consisting of NR5R6, or5, oc(=o)r7, c(=〇)OR5, c(=o)r5, yl, C2-C8 Substituted by a substituent of a dilute group, a c2-c8 alkynyl group, a c3-C8 ring-based group, a CVCe haloalkyl group, and a CrC:8 alkoxy group; each of R5 and R6 is independently hydrogen or an alkyl group; R7 is C--C8, 〇Κ·5, or nr5r6; m is 1-12; and η is 1-12. In the present invention, cyclohexenone compound 1 can change sputum cell activity, and in AcP -IgAN mice prevent renal inflammatory response, so an exemplary cyclohexenone compound of the invention is suitable for slowing IgAN » specific embodiments of the invention ' A method for alleviating a subject immunoglobulin type A nephritis (IgAN) comprising: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, or a precursor drug to the host, wherein the cyclohexenone compound has the following structure: 201247612

Wherein 'each X and Y are each independently oxygen, NR5, or sulfur; R is hydrogen, or c(=o)crc8 alkyl; each R丨' R2, and R3 are each independently hydrogen, methyl Or (CH2)m_CH3; R4 is NR5R6, or5, oc(=o)r7, c(=o)or5, c(=o)r5, halogen, 5 or 6 membered ring lactone, C,-C8 alkane a c2-c8 alkenyl group, a c2-c8 alkynyl group, an aryl group, or a glucosyl group, which is a '5 or 6 membered ring lactone, a Ci-Cs alkyl group, a c2-c8 alkenyl group, a CrC8 alkynyl group, an aryl group. And one or more selected from the group consisting of NR5R6, 〇R5, 〇C(=〇)R7, C(=〇)〇R5, C(=〇)R5, c,-c8 alkyl, C2 Substituting -C8 dilute, c2-c8 block, 〇3-(: 8-ring, CrC8 haloalkyl, and Ci-C8 alkoxy; each R5, and Re are each independently hydrogen Or C "C8 alkyl; R7 is cvc8, 〇r5, or nr5r6; m is 1-12; and η is 1-12 » specific terminology, unless otherwise stated, the term used in the present invention, including instructions And the terms used in the scope of the patent application are defined as follows. It should be understood that the present invention is The book and the application for the second: the number "1" 9 "this" also includes the plural meaning. Unless otherwise specified, any conventional methods, including mass spectrometry, calendar 'HPLC, protein chemistry, biochemical technology, Recombinant Brain 42 201247612 Technical and pharmacological techniques can be used in the present invention. Further, unless otherwise stated, the use of "or" or "and" means "and/or". And "including" are meant to be non-limiting. In addition, the headings of the various paragraphs of the present invention are for illustrative purposes only and are not intended to limit the subject matter of the present invention. The alkyl group may be a saturated alkyl group (meaning that it does not contain any carbon-carbon double bond or carbon-carbon triple bond), or the alkyl group may be an unsaturated alkyl group (meaning that it contains at least one carbon) · Carbon double bond or carbon-carbon triple bond). Whether it is a saturated or unsaturated alkyl group, it may be a branched or linear alkyl group. The "alkyl" group may have 1 to 10 carbons. Atom; even if the invention also includes an "alkyl" group of undefined numerical ranges In any case, the numerical range such as "丨 to (7)" means each integer in the range; for example, "丨 to (7) carbon atoms" means that the alkyl group may be 1 carbon atom, 2 carbon atoms, 3 A carbon atom or the like, and composed of at most 10 carbon atoms. The alkyl group of the compound of the present invention may be defined by "0丨-(:6 alkyl group) or other similar definitions. For example (for illustration only) '"CrCei alkane By "alkyl" is meant one, two, three, four, five, or six carbon atoms in the alkyl chain. Further, one embodiment of the alkyl group is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-buty(R), and butyl (t-butyl). The group that makes up. Typical alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl 'butyl, isobutyl, sec-butyl, tert-butyl, pentyl' neopentyl, hexyl, alkene Propyl, 2-butenyl, 3-butenyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentyl hydrazine 43 201247612 base, % hexylmethyl, and the like. In one embodiment, the complete system is a cvc6 alkyl group. "Asian base" sSJ refers to a divalent alkyl radical. Any of the above monovalent alkyl groups can form an alkenyl group by removing a second hydrogen atom from the alkyl group. In one embodiment, the alkylene group is c, -c: 6 alkylene. In another embodiment, the alkylene group is a stannylene group. Typical mercapto groups include, but are not limited to: _CH2_, -CH(CH3)- '-C(CH3)2- '-CH2CH2- '-CH2CH(CH3)- ' •CH2C(CH3)2-,- CH2CH2CH2-, -CH2CH2CH2CH2-, and the like. In the present invention, the term "aryl" means an aromatic ring in which each atomic system forming an aromatic ring is a carbon atom. The aromatic ring may be formed by five, six, seven, eight, nine, or more than nine carbon atoms. In addition, the aromatic ring can be optionally substituted. In one embodiment, the aryl group is phenyl or naphthyl. In one embodiment, the aryl group is a phenyl group. In one embodiment, the aryl group is a C6_C(7) aryl group. The aryl group may be a single radical or a pair of free radicals. Base (ie, arylene) "» In addition, in one embodiment, the arylene system is a Ce-Cio arylene. Examples of arylene include, but are not limited to, 丨2 phenyM, 2-ene), 1,3-phenylene (phenyi_i, 3_ene), and ι,4-phenylene (phenyl- l,4-ene) 〇 "aromatic ring" refers to a non-localized 71 A planar ring of an electronic system in which the non-localized subsystem includes a single electron and the n is an integer. The aromatic ring may consist of five, six, seven, eight, nine, ten, or more than ten atoms. In addition, the aromatic ring can be optionally substituted. "Aromatic ring" 44 201247612 The term includes: carbocyclic aryl ("aryl", such as "heteroaryl" or "heteroaromatic group") group (di-cyclic aryl (or "aromatic ring") The word is also ^ ^ pyridine group). In addition, '-k:) (ie, the ring of the (four) carbon atom pair) f (fUSed-rmg, ... "South", "dentate", or "dentate" - The term “fluorine, gas, bromine, or iodine.” The term “in-loop vinegar” refers to the ring-cooled class, which is a condensation product of homo- and rebel-COOH. It is a closed loop composed of two or more carbon atoms and one oxygen atom and has a network group = 〇 on a carbon atom adjacent to the milk. Heterocyclic"-word system has one to four hybrids in the ring + a heteroaromatic ring (ie, a heteroaryl group) and a heterocycloalkyl group, wherein each hetero atom in the ring is selected from the group consisting of 0, S, and N, and each of the heterocyclic groups in the ring system has 4 to 1 〇 atom, but any ring does not contain two adjacent 〇 or 3 atoms. The ring system of the non-aromatic heterocyclic group (ie, 'heterocycloalkyl group) includes a group having only 3 atoms. Aromatic heterocyclic group The ring system is required to have at least 5 atoms. The heterocyclic group includes a benzo fused ring system. An example of a 3-membered heterocyclic group is an aziridinyl group. An example of a group is azetidinyl. An example of a 5-membered heterocyclic group is thiazoly!. An example of a 6-membered heterocyclic group is pyridyl (pyridyl), and 1 member An example of a heterocyclic hydrazine is quinolinyl. Examples of non-aromatic heterocyclic groups include: pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl ), tetrahydrofuran sold phenethyl ([11&11;(1|"〇1;11丨611丫1), °恶*坐炫1 ketone group (〇乂32〇11<1111〇11)^ ), four 201247612 i ° tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl 'thio? Thiomorpholinyl, thioxanyl, piperazinyl, aziridinyl, azadipine (azetidi) Nyl), oxetanyl, thietanyl, homopiperidinyl, oxepanyl, thiepanyl, oxa Oxepinpinyl, diazinyl, thiazepinyl, 1,2,3,6-tetra-argon beta ratio bite (l, 2, 3) , 6-tetrahydropyridinyl), 2-0 pyrololin-2-yl, 3-pylorin-3-yl, dihydro-β-indolinyl, 2Η-β 2H-pyranyl, 4Η-β aryl (4H-pyranyl), II. Dioxanyl, 1,3-dioxolanyl, ° ratio "pyrazolinyl, dithianyl, dithiolanyl ), dihydrogen. Dihydropyranyl, dihydrothienyl, dihydrofuranyl, ° ratio "pyrazolidinyl, ° meter. Imidazolinyl, °m" imidazolidinyl, 3-azabicyclo[3.1.0]hexane (3-azabicyclo[3.1.0]hexanyl), 3-azabicyclo[4.1 .0] heptyl (3-azabicyclo [4.1.0] heptanyl), 3H-0 indole (3H-indolyl), and quinoliziny 1 (quinoliziny 1). Examples of aromatic heterocyclic groups include: β-pyridinyl, taste. Iridazolyl, pyrimidinyl, 0 to 0 pyrazolyl. Plug. Triazolyl, pyrazinyl, tetra 46 201247612 tetrazolyl, furyi, thienyi, isoxazolyl' thiazolyl, azole Oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzo Benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, anthraquinone. Pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl 'oxadiazolyl' thiadiazolyl 0, furazanyl, benzo bite. Benzofurazanyl, benzothiophenyi, benzothiazolyl, benzoxazolyl, hydrazine. Sitting on quinazolinyl, quinoxalinyl, naphthyridinyl, and shouting "furopyriclinyl. If possible, the aforementioned groups may be C-linked or N-linked. For example, the group derived from pyrrole may be pyrrol-1-yl (N-linked), or pyrrole-3-yl (C-linked). Further, the group derived from imidazole may be imidazol-1-yl or Imidazolyl-3-yl (all N-linked), or imidaz-2-yl, tat-4-yl or imidazo-5-yl (all C-linked). Heterocyclic groups include benzo-fused ring systems. # aromatic heterocyclic ring may be substituted by one or two oxygen groups (=0), such as pyrroline-2-copper (p:yrrolidin" 2-one) 0 combined therapy, generally speaking, the invention The composition (the composition used in combination therapy), and other agents do not necessarily need to be administered with the same pharmaceutical composition, and in some embodiments, due to the physical and chemical properties of the agent, 47 r 201247612 Different routes of administration. In the case of partial injection, the first administration is based on the known method of cardiac medicine, and the clinician will then modify the dosage and form of administration and the number of administrations based on the observed effect. In some embodiments, the effective therapeutic dose can be varied when the drug is combined. In addition, the combined treatment includes interval treatment between multiple doses at the beginning and end, which helps the patient to manage clinical treatment. In the combination therapy described in the present invention, the total dose of the compound to be administered may be varied depending on the form of the compound to be used, the particular drug used, the disease, the condition of the disorder, or the condition to be treated. It will be appreciated that in some embodiments, the medical treatment used to treat, prevent or ameliorate symptoms for soothing may vary depending on a variety of factors. These factors include the disease that the subject's subject is infected with, and the age, weight, sex, diet, and medication of the subject. Therefore, in other embodiments, the medical treatment actually varies greatly, and thus the treatment method of the present invention may also be changed. The compound (i.e., the cyclohexenone compound of the present invention) and other solid enzymes and/or immunosuppressive agents are also included in the present invention. In some embodiments, immunosuppressive agents include, but are not limited to, Glucocorticoids, cytostatics, anti-Zhao, drugs that act on immunophilins, and other drugs, such as interferons. (interferon), opport (interferon), TNF-binding protein, and mycophenolate. Some embodiments of the present invention provide an early treatment for nephropathy (including glomerulosclerosis, renal glomerulonephritis, and the like) Pharmaceutical composition, 48 201247612 includes: an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, or a prodrug thereof; and one or more sterols and / or an immunosuppressive agent, wherein the cyclohexene oxime compound has the following structure:

Wherein each X and Y system is independently oxygen, NR5, or sulfur; R is hydrogen, or C(=0)C, -C8 alkyl; each R wide R2, and R3 are each independently hydrogen, Methyl or (CHdm-CHs; R4 is NR5R6, OR5, 〇C(=〇)R7, C(=0)0R5, C(=0)R5, halogen, 5 or 6 membered vinegar, Ci- Cg Hyun, C2_Cs dilute 'C2_C8 blocky' aryl, or glucosyl, wherein 5 or 6 membered ring lactone, C "C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, aryl, And one or more selected from the group consisting of NR5R6, 〇r5, oc(=o)r7, c(=o)or5, C(=0)R5, Cl-c8 alkyl, c2_c8, C2 Substituted by a substituent of -C8 alkynyl, CVC: 8 cycloalkyl, c丨-Cs haloalkyl, and c丨-C8 alkoxy; each R5, and R0 are each independently hydrogen, or €1 ( : 8 alkyl; R7 is (: 丨-C8 alkyl, 〇R5, or NR5R6; m is 1-12; and n is 1-12. In some embodiments, the nephropathy is glomerulosclerosis (eg, FSGS) In other embodiments, the nephropathy is renal glomerulonephritis (eg, immunoglobulin type A glomerulonephritis (igAN)). A class of steroid hormones that bind to the glucocorticoid receptor (GR). The term cortisol is derived from its regulation in glucose metabolism and its synthesis 49 201247612 in the adrenal cortex ( Adrenal cortex) and its steroid structure. Examples of auditory corticosteroids include, but are not limited to, cortisol (cortisol), cortisone acetate, prednisone, prednisone Prednisolone, methylprednisolone, dexamethasone, betamethasone, triamcinolone, beclometasone, fluorohydrogen acetate Fludrocortisone acetate, deoxycorticosterone acetate (DOCA), and aldosterone. Examples of drugs that act on immunones include, but are not limited to, cyclosporin, tac Tacrolimus, voclosporin and other calcineurin inhibitors, and rapamycin (siro) Limus) β Pharmaceutical Composition/Dosage Form The term "acceptable" means that the agent, composition, or active ingredient of the present invention does not cause a continuing adverse reaction to the daily life of the subject. Burdock is a fungus of the family Meripilaceae. The body of the burdock is generally flat or grows outward from the growth surface, and the sub-solid layer is oriented outward; in addition, the edges may be slightly raised and appear in a small bracket. Most of the species of Antrodia camphorata grow in the northern temperate forest and cause the brown rot of trees. In addition, some of the special species of this fungus are more effective, and are often used as one of the traditional Chinese medicines in Taiwan. As used herein, the term "carrier" refers to a relatively non-toxic compound or chemical that aids in the delivery of a compound to a cell or tissue. 50 201247612 In the present invention, the term "co-administered" includes the administration of a selected therapeutic agent to a patient, and further includes a method of treating the agents in the same or different administration manners, or at the same or different administration times. The term "diluent" means a compound used to dilute the compound used prior to administration. Diluents can also be used to stabilize compounds because they provide a more stable environment. Salt buffer solutions commonly used in the art (which can be used to control or maintain pH) can also be used as diluents including, but not limited to, citrate buffer solutions. In the present invention, the term "effective dose" or "therapeutically effective dose" means an appropriate dose of the agent or compound which, to some extent, alleviates one or more conditions of the disease or condition being treated. In this way, the symptoms, symptoms, or causes of the disease can be alleviated and/or alleviated, or other changes can be made to the physiological system according to the needs. The "effective dose" used in the treatment of the disease means that the disease can be clinically provided. Significantly improved compositional doses required 'where the composition is a system comprising the compounds disclosed herein. In addition, appropriate "effective" doses are determined according to methods such as dose escalation tests, under different conditions. In the present invention, the term "promotional enhancement" refers to the effect or duration of an increase or extension of a predetermined effect. ^ Bellow, therefore, the term "promotion" or "擗%^„9" refers to the dragon that increases or prolongs the effectiveness or duration, or the line. Other therapeutic agents in the treatment can achieve an effect of increasing or prolonging. Further, "enhanced effective dose" as used in the present invention means an appropriate dose which can enhance the effect of another therapeutic agent in a predetermined system. 5] 201247612 In the present invention, the term "metabolite" refers to a compound derivative formed by metabolism of a compound. The term "active metabolite" refers to a physiologically active compound derived from the metabolism of a compound. Things. Further, in the present invention, the term "metabolism" refers to all processes in which a specific component is changed by an organism (including, but not limited to, hydrolysis reaction and enzyme catalytic reaction). Therefore, 'enzymes can make special structural changes to a compound. For example, cytochrome Ρ450 can catalyze a variety of oxidation and reduction reactions, while uridine diphosphate glucuronyltransferase catalyzes the transfer of active glucuronic acid molecules to aromatic alcohols, fatty alcohols, Carboxylic acids, amines, and sulphydryl radicals are trapped. In the present invention, the metabolite of the compound is also selectively permeable: it is defined by administering the compound to a host and analyzing the tissue sample of the host, or culturing the compound with liver cells in vitro and analyzing the resulting compound. In the present invention, the term "pharmaceutical combination" means a product formed by mixing or combining more than one active ingredient, and comprises both fixed and non-fixed compositions of the active ingredient. Here, the term "fixed composition" means that the active ingredient (a compound such as the cyclohexanone compound of the present invention) and an auxiliary agent are simultaneously administered to a patient in a single object or dosage form. The term "non-fixed composition" means that the active ingredient (a compound such as the cyclohexenone compound of the present invention) and an adjuvant are administered in separate dosage forms simultaneously, together, or without specific time intervals. A patient in which such a mode of administration provides an effective amount of two compounds 52 201247612 to a patient. In addition, non-fixed compositions can also be used in cocktail therapy, such as by administering three or more active ingredients. The term "pharmaceutical composition" means a mixture of a compound (ie, a cyclohexenone compound of the present invention) and other chemical components, such as a carrier, a stabilizer, a diluent, a dispersant. , suspending agents, thickeners, and/or excipients. Pharmaceutical compositions can help a compound be administered to a species. Various techniques for administering compounds known in the art to which the present invention pertains include, but are not limited to, intravenous, oral, spray administration, parenteral administration (non-digestive administration), ocular administration, pulmonary administration (inhalation administration). And external use of drugs. In addition, the term "subject" or "patient" includes mammals; examples of mammals include, but are not limited to, any species of the lactation network: humans, non-human primates such as orangutans and other apes and monkey species; farms Animals such as cattle, horses, sheep, goats, pigs; livestock such as rabbits, dogs, and cats; experimental animals including scorpion animals such as rats, mice, guinea pigs, and other similar animals. In one embodiment, the mammalian system is a human. In the present invention, the term "treatment" includes: preventing or inhibiting other diseases by inhibiting and/or treating at least one condition for alleviating, alleviating or ameliorating a disease or symptom (for example, preventing the occurrence of a disease or symptom), Alleviate the symptoms or symptoms that cause (4) or symptoms to be caused by symptoms or symptoms, or to inhibit the disease or symptoms. The route of administration is not limited to: oral administration, ocular, lung, mucosa, and the administration routes suitable for the present invention include intravenous injection, intestinal tract, spray type, parenteral, 201247612 skin surface, vagina, ear, nasal cavity, And external use of drugs. In addition, examples of parenteral administration include intramuscular, subcutaneous, intravenous, intrathecal injections, and also include intracerebral meninges, direct intraperitoneal, intraperitoneal intralymphatic, intranasal injections. In a particular embodiment, the compounds described herein are generally prepared as a depot or sustained release dosage form' and are administered in a local rather than systemic manner, e.g., by injecting the compound directly into an organ. In a particular embodiment, a long-acting dosage form of the drug can be administered by means of colonization (e.g., subcutaneous or intramuscular) or intramuscular injection. Further, in other embodiments, the drug can be administered by a standard dry drug delivery system (e.g., a liposome coated with an organ-specific anti-Zhao). In this embodiment, the liposomes can be directed to an organ and selectively absorbed by the organ. In other embodiments, the compounds of the invention may be prepared in a fast-release dosage form, a slow release dosage form, or an immediate release dosage form. In other embodiments, the compounds of the invention may be administered in a topical manner. Pharmaceutical Composition/Life [Type In some embodiments, the compounds of the present invention can be prepared as a pharmaceutical composition. In a particular embodiment, the pharmaceutical composition can be prepared in a conventional manner using one or more physiologically acceptable carriers; and the physiologically acceptable carrier includes excipients and adjuvants which aid in the processing of the active compound The process is prepared to produce a pharmaceutically acceptable agent. The appropriate dosage form is chosen according to the route of administration. Any pharmaceutically acceptable technique, carrier, and excipient can be used to prepare the pharmaceutical compositions of the present invention: Remington. The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa.: Mack Publishing Company, 54 201247612 1995); Hoover, John E., Remington's Pharmaceutical •Scz.ewce·?,Mack Publishing Co., Easton,Pennsylvania 1975; Liberman, HA and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York , NY, 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkinsl 999). The present invention provides a pharmaceutical composition comprising a compound (e.g., a cyclohexenone compound of the present invention) and a pharmaceutically acceptable diluent, excipient, or carrier. In a particular embodiment, The compound can be administered by a combination of a compound (e.g., a cyclohexenone compound of the present invention) and a pharmaceutical composition of another active ingredient in a combined therapeutic manner. The present invention includes all compositions of the present invention relating to the active ingredients described in the paragraphs of the Combination Therapy. In a particular embodiment, the pharmaceutical composition comprises one or more compounds (e.g., a cyclohexenone compound of the invention). The pharmaceutical composition of the present invention refers to a mixture of a compound (e.g., a cyclohexenone compound of the present invention) and other compounds, such as a carrier, a stabilizer, a diluent, a dispersing agent, a suspending agent, and a thickening agent. And/or excipients. In a particular embodiment, the pharmaceutical composition can facilitate administration of the compound to an organism. In some embodiments, the therapeutic method of the present invention is to administer a therapeutically effective amount of a compound (eg, a cyclohexenone compound of the present invention) as a pharmaceutical composition to a subject having a disease or symptom. . In a particular embodiment, the mammalian system is a human. In a particular embodiment, the therapeutically effective dose will vary depending on the severity of the disease, the age of the subject and the extent of the health, the potency of the compound, and other factors. Furthermore, the compounds described in the present invention can be used alone or in combination with one or more therapeutic agents (as a component of a mixture). In one embodiment, the compound (e.g., the cyclohexenone compound of the present invention) is prepared in the form of an aqueous solution. In certain embodiments, examples of aqueous solutions may be selected from water-soluble, physiologically compatible buffers (such as Hank's solution, Ringer's solution, or physiological saline). In the embodiments, the compound (e.g., the cyclohexenone compound of the present invention) can be prepared into a mucosal dosage form. In a specific embodiment, the mucosal administration form includes a penetrant that can properly penetrate the mucosal barrier. In other embodiments, the compounds described herein are prepared in other parenteral dosage forms and suitable dosage forms include aqueous or non-aqueous solutions. In particular embodiments, such solutions include physiologically compatible buffers and / or an excipient. In another embodiment, the compound of the present invention can be prepared into an oral dosage form. Here, the compound of the present invention (i.e., the cyclohexenone compound of the present invention) is contained. The preparation is carried out by mixing the active compound with, for example, a pharmaceutically acceptable compound or an excipient. In various embodiments, the compound of the present invention can be prepared into an oral dosage form. Examples include lozenges, powders, tablets, pills, capsules, syrups, gels, medicated syrups, elixirs, steroids, suspensions, and the like. In a particular embodiment, the oral dosage form can be one or more solids. The excipient is mixed with one or more of the compounds of the present invention, and the resulting mixture is selectively milled, and if necessary, the powder mixture can be processed to obtain a tablet or pill core after addition of a suitable adjuvant. Suitable excipients are, in particular, fillers, such as sugars containing lactose, sucrose, mannitol, 56 201247612 or sorbitol; cellulose preparations such as maize starch, wheat flour, rice starch, potato starch, gelatin , rubber gum, sulfhydryl cellulose, microcrystalline cellulose, hydroxypropyl decyl cellulose, sodium carboxymethyl cellulose; or other such as polyvinylpyrrolidine (PVP or povidone) or calcium phosphate beta In the examples, 'disintegrator may be optionally added. Examples of the disintegrant may include: Croscarmellose sodium, polyethylene bismuthone, agar Or alginate or a salt thereof (such as sodium alginate). In one embodiment, the agent such as the core of the pill and the lozenge may be one or more suitable coating layers. In a specific embodiment, the concentrated sugar solution is used. To encapsulate the agent. The saccharide solution may optionally include other additional ingredients such as gum arabic, talc, polyvinylpyrrolidone carbopol gel, polyethylene glycol, and/or titanium dioxide; a coating solution; and a suitable organic solvent or solvent mixture β dye and/or pigment may also be selectively added to the coating for identification purposes. In addition, dyes and/or pigments may also be selectively used to A composition for labeling different active compound agents. In a particular embodiment, a therapeutically effective amount of at least one compound of the invention can be prepared in a form other than an oral dosage form. The oral dosage form comprises a push-fit capsule made of gelatin (10), a sputum, and a soft and sealed capsule made of gelatin and a plasticizer such as glycerol or sorbitol. In a particular embodiment, the push-fit capsule comprises an active ingredient in admixture with one or more fillers. Examples of the filler may include lactose, an adhesive such as starch, and/or a lubricant such as talc or magnesium stearate, and optionally include a stabilizer. In other embodiments, the soft capsules comprise an active compound dissolved or suspended in a suitable liquid in the form of 57 201247612 or above. Examples of suitable liquids include: one or more fatty oils, liquid paraffin, or liquid polyethylene glycol. Further, a stabilizer may be optionally added. In other embodiments, a therapeutically effective dose of at least one compound of the invention can be prepared in the form of a buccal dosage form or a sublingual dosage form. Examples of suitable dosage forms for oral or sublingual administration include lozenges, tablets, or gels. In still other embodiments, the compounds of the invention may be prepared as parenteral injection forms' which include dosage forms suitable for bolus injection or continuous infusion. In a particular embodiment, the injectable dosage form is in unit dosage form (e.g., in the form of an ampoule), or in a multi-dose package. In addition, a preservative can be optionally added to the injectable dosage form. In still other embodiments, the pharmaceutical composition of the compound (ie, the cyclohexenone compound of the present invention) is dissolved in an oily or aqueous vehicle to prepare a sterile suspension, solution, or emulsifier. A dosage form for parenteral injection. Parenteral injection forms may optionally include such agents as suspending, stabilizing, and/or dispersing agents. In a particular embodiment, the pharmaceutical dosage form for parenteral administration comprises an aqueous solution of the active compound in a water soluble form. In other embodiments, the suspension of the active compound is prepared as a suitable oily injection suspension, as an example of a suitable oil-soluble solvent or vehicle for use in the pharmaceutical compositions of the invention, and may include a fatty oil such as sesame oil, or For example, ethyi eleate or a synthetic fatty acid ester of triglyceride, or a liposome. In a particular embodiment, an aqueous injection suspension contains a substance that increases the viscosity of the suspension, such as carboxy hydrazine. Cellulose sodium, sorbitol, or dextran. In addition, the suspension optionally includes suitable stabilizers or agents to enhance the dissolution of the compound to provide a highly concentrated solution. Alternatively, in other embodiments, the active ingredient may be in powder form for mixing with a suitable vehicle (e.g., sterile pyrogen-free water) prior to use. In one embodiment, the compound (i.e., the cyclohexenone compound of the present invention) is prepared as a solution for parenteral injection by the method of the present invention or by methods known in the art, and an autoinjector is used. Dosing. Automated injections are disclosed in U.S. Patent Nos. 4,031,893, 5,358,489, 5, 540, 664, 5, 665, s. 71, 5, 695, 472, and WO/2005/087297, each of which is incorporated herein by reference. The contents are incorporated herein by reference. In general, all autoinjectors include a solution of hips to be injected, the solution comprising a compound (ie, the cyclohexenone compound of the present invention. In addition, the autoinjector system includes: one for containing a solution The storage space 'this storage space is fluidly connected to a needle for administration; and the automatic insertion needle mechanism for inserting the needle onto a patient to deliver the medicament to the patient. For example, the syringe can be supplied for about 0.3. mL, 0.6 mL, 1.0 mL, or other suitable volume of solution, and the mother 1 ml of the solution contains a compound having a concentration of about 5 mg to 50 mg (i.e., the cyclohexenone compound of the present invention). Each of the syringes may deliver only one dose of the compound. In still other embodiments, the compound (ie, the cyclohexanone compound of the present invention) may be administered externally. Here, the compounds of the present invention can be prepared into various types. Compositions which can be administered externally, such as solutions, suspensions, emulsions, gels, slurries, sticks, ointments, creams, ointments, etc. In addition, such a medicine 59 201247612 pharmaceutical composition Optionally, it contains a solubilizing agent, a stabilizer, a tonicity enhancing agent, a buffering agent, or a preservative. In a further embodiment, the compound (ie, the cyclohexenone compound of the present invention) can be skin In a specific embodiment, the dermal absorption dosage form may be a skin administration device or a skin administration patch, and may be an oil-soluble emulsifier, or a buffered aqueous solution dissolved and/or dispersed in a polymer or an adhesive. In various embodiments, such patches are used for sustained, intermittent, or on demand. In other embodiments, the skin of the compound (ie, the cycloheximide compound of the present invention) For the broad absorption mode of administration, an iontophoretic patch and similar patches can be used. In a particular embodiment, the skin-absorbing patch can control the delivery of a compound (ie, the cyclohexenone of the present invention) Compounds. In certain embodiments, slowing down the rate of absorption can be achieved by using a rate controlling film, or by confining the compound to a polymer matrix or gelatinous vessel. In one embodiment, an absorption enhancer can also be used to aid absorption. The absorption enhancer or carrier can include a pharmaceutically acceptable solvent that can aid in the passage of the compound through the skin. For example, in one embodiment, a 'skin delivery device The invention is in the form of a bandage comprising: a back film; a storage space for accommodating the compound and selectively accommodating the carrier; and a selective rate control barrier for delivering the drug to the drug for a long time at a controlled and predetermined rate to The body of the body is widened; and a security element to ensure the safety of the device to the skin. The skin absorbent dosage form of the present invention can be administered using a variety of devices known in the art. Examples of devices can include, but are not limited to, the United States. Patent Nos. 3,598,122, 3,598,123, 3,710,795, 201247612 3,731,683, 3,742,951, 3,814,097, 3,921,636, 3,972,995, 3,993,072, 3,993,073, 3,996,934, 4, 〇31,894, 4,060,084, 4, 〇69,307, 4,077,407, 4,201,211 No. 4,230,105, No. 4,292,299, No. 4,292,303, No. 5,334,168, No. 5,665,378, No. 5,837,280, No. 5,869,090, No. 6,923,983, No. 6,929,801, No. 6,946,144 and second of said apparatus. The broadly absorbing dosage forms of the present invention may comprise specific pharmaceutically acceptable excipients known in the art. In one embodiment, the skin-absorbing dosage form of the present invention comprises at least three components: (1) a compound agent (ie, a cyclohexenone compound of the present invention); P) an absorption enhancer; and (3) ) aqueous adjuvant. In addition, the skin absorbent dosage form can include other ingredients such as, but not limited to, a gelling agent, a cream or ointment base, and the like. In some embodiments, the skin absorbent dosage form further comprises a woven or non-woven backing pad material to aid in absorbing and preventing detachment of the skin absorbent dosage form from the skin. In other embodiments, the skin absorbent dosage form of the present invention is maintained Saturated or oversaturated state' to help the agent spread into the skin. In other embodiments, the compound (i.e., the cyclohexenone compound of the present invention) can be prepared for administration by inhalation. A variety of dosage forms suitable for inhaled administration include, but are not limited to, spray, moisture or powder form. The pharmaceutical composition of the compound (ie, the cyclohexenone compound of the present invention) is generally a pressurizing device or a sprayer' and is used in combination with a suitable propellant (eg, digas-fluorine, trigas) The monofluorosilane, dioxane tetrafluoroethane, carbon dioxide, or other suitable gas) form a mist spray for administration. In the specific 201247612 embodiment, the unit dose of the calendar spray is determined by the valve to deliver the dose supplied by the meter. Gelatin capsules and storage packs (for illustrative purposes only) used in the "inhaler or insufflator" in a particular embodiment can be prepared as a powder mixture containing a compound and a suitable powder base such as lactose or powder. The intranasal administration form is a dosage form known in the art and is described in U.S. Patent Nos. 4,476,116, 5,116,817, and 6,391,452, each of which is incorporated herein by reference. . A solution of physiological saline can be prepared according to the above method or other agents prepared by methods known in the art, wherein the agent comprises a compound (i.e., the cyclohexenone compound of the present invention) and the solution Benzyl alcohol or other suitable preservatives, fluorocarbons, and/or other solubilizing or dispersing agents known in the art may be included. For example, refer to Ansel, H.C. ei α/.

Preferably, such compositions and agents are prepared with suitable non-toxic pharmaceutically acceptable ingredients. These components can be referred to reference materials commonly used in the art, such as REMINGTON: THE SCIENCE AND PRACTICE PHARMACY, 21st edition, 2005. In addition, the carrier may be suitably selected depending on the desired formulation of the dosage form in the nasal cavity, such as a solution, suspension, ointment, or gel. Intranasal administration usually contains a large amount of water and active ingredients. In addition, minor amounts of other ingredients such as pH adjusting agents, emulsifiers or dispersing agents, preservatives, surfactants, gelling agents, or buffering agents, and other stabilizers and solubilizing agents may be included. Preferably, the intranasal administration mode has an isotonic pressure with the nasal secretions. When administered by inhalation, the compounds of the invention may be prepared as a spray, moisture or powder. The pharmaceutical composition of the present invention is generally a 62 201247612 pressurizing device or a sprayer, and is used in combination with a suitable propellant (eg, di-halogenated difluoromethane, tri-gas-fluorodecane, dichlorotetrafluoroethylene). The alkane 'carbon dioxide, or other suitable gas), forms a mist spray for administration. In the case of a pressurized spray, the unit dose is determined by a valve to deliver a metered dose. In addition, gelatin capsules and storage packs (for example only) used in inhalers or insufflators can be prepared as a powder mixture containing a compound of the present invention and a suitable powder base such as lactose or starch. In still other embodiments, the compound (ie, the cyclohexenone compound of the present invention) can be prepared into a rectal composition such as an enema, a rectal gel, a rectal foam, a rectal spray, a suppository, or a colloid. A suppository, or a retention enemas, which comprise a conventional suppository base (such as cocoa butter or other glycerides), and synthetic polymers (such as polyvinylpyrrolidone, PEG, and the like). Further, in the suppository dosage form of the composition, the cocoa butter can be selectively used with a low melting point (e.g., but not limited to a mixture of a fatty acid and a glyceride), and the low solubility point first melts. In a particular embodiment, the pharmaceutical composition is prepared by any conventional means with one or more physiologically acceptable carriers, wherein the physiologically acceptable carrier includes excipients and adjuvants which aid in the active compound. It is prepared and applied to medicine. In addition, an appropriate dosage form can be selected according to the selected route of administration. Any pharmaceutically acceptable technique, carrier, and excipient can be optionally employed, where applicable and in accordance with what is known in the art. A pharmaceutical composition comprising a compound (i.e., a cyclohexenone compound of the present invention) can be prepared by a conventional method, for example, by way of example only, a conventional mixture, 63 201247612 dissolution, grinding, pelleting, powdering, Emulsified, made into capsules, coated or pressed. The pharmaceutical composition may comprise: at least one pharmaceutically acceptable carrier, diluent or excipient; and at least one compound of the invention (ie, a cyclohexenone compound of the invention) which is An active ingredient. The active ingredient is in free acid or free form or in the form of a pharmaceutically acceptable salt. Furthermore, the methods and pharmaceutical compositions of the present invention include crystalline forms (i.e., polymorphs) and also include active metabolites of such compounds having the same activity. Tautomers of the compounds described herein are also included within the scope of the compounds described herein. Further, the compounds of the present invention may also be in a non-solvent form, as well as a solvent form, wherein the solvent form is a pharmaceutically acceptable solvent such as water, ethanol, and the like. In the present invention, the solvent form of the compound is also included in the scope of the present invention. In addition, the pharmaceutical composition may optionally include other drugs or agents, carriers, adjuvants (such as preservatives, stabilizers, moisturizers, or emulsifiers), solution accelerators, salts for adjusting osmotic pressure, and buffers. Liquid, and / or other therapeutically effective substances. In the present invention, the preparation method of the composition containing the compound of the present invention comprises: preparing the compound into a solid state with one or more low-activity and pharmaceutically acceptable excipients or Semi-solid or liquid form. Solid compositions include, but are not limited to, powders, money, dispersed granules, capsules, and suppositories. The liquid composition includes: a solution in which a compound is dissolved; an emulsion containing a compound; or a solution containing a liposome, a colloidal particle, or a nanoparticle, wherein the microlipid, „particle, or nanoparticle internal system is accommodated 64 201247612 There is a compound according to the present invention. The semi-m composition includes, but is not limited to, a gel, a suspension, or a cream. The form of the pharmaceutical composition of the present invention may include: (4) a solution or suspension, It can be used to form a solution or suspend the solid form or emulsion in liquid Zhao before use. These compositions can also be selected as 1± containing non-toxic auxiliary agents such as humidifying agents or emulsifiers, pH buffering agents, etc. In some embodiments, the pharmaceutical composition of the present invention comprising at least one compound (ie, the cyclohexenone compound of the present invention) is in a liquid form, wherein the agent is in solution In the middle, in the suspension, or both. In general, when the composition is administered as a solution or suspension, the first part of the agent is in the form of a solution, and the second part of the agent has a special form, such as In liquid matrix The liquid composition in some embodiments includes a gel dosage form. In other embodiments, the liquid composition is in the form of an aqueous solution. In a particular embodiment, the pharmaceutical aqueous suspension comprises one or more polymers, The polymer as a suspending agent may include a water-soluble polymer such as a cellulose polymer (e.g., hydroxypropylmethylcellulose), and a water-insoluble polymer such as a crosslinked carboxyl group-containing polymer. Specific pharmaceutical compositions include mucoadhesive polymers, such as: methyl cellulose, carbomer (acrylic acid polymer), poly(methyl methacrylate), Polyacrylamide, polycarbophil (p〇lycarb〇phil), acrylic acid/acrylic acid butyl vinegar copolymer, sodium alginate, and glucomannan. 65 201247612 Pharmaceutical compositions are also selectively included a solvent to aid in the solubility of the compound (i.e., the cyclohexenone compound of the present invention). The term "solubilizer" generally includes: one can be used to form a micellar solution. Reagent, or a reagent solution. In addition, a specific acceptable nonionic surfactant such as polysorbate 80 can also be used as a solubilizing agent, and the solubilizing agent can also be an ocularly acceptable diol or polyglycol (eg, Polyethylene glycol 400), and glycol ethers. Further, the pharmaceutical composition may optionally include one or more pH adjusters or buffers. Wherein, the pH adjusting agent or buffering agent comprises: an acid such as acetic acid, boric acid, citric acid, lactic acid, phosphoric acid, hydrogen acid; such as sodium hydroxide, sodium phosphate, sodium borate, sodium citrate, sodium acetate, sodium lactate, tris-hydroxyl Tris-hydroxymethylaminomethane and the like; and buffer substances such as citrate/dextrose, sodium bicarbonate, and ammonium hydride. The amount of such acid, test, and buffer materials is an acceptable range to maintain the pH of the composition. Further, the pharmaceutical composition may optionally include one or more salts which are required to maintain the osmotic pressure of the composition within an acceptable range. Salts which may be used include: sodium, potassium, or ammonium cations; and gas, citrate, ascorbate, borate, phosphate, bicarbonate, sulfate, thiosulfate, And anions of sulfite. Further, examples of suitable salts include: sodium gasification, potassium hydride, sodium thiosulfate, sodium sulfite, and ammonium sulfate. Other pharmaceutical compositions may optionally include one or more preservatives to inhibit bacterial activity. Suitable preservatives include: mercury-containing substances such as merfen 66 201247612 and thiomersal; stable chlorine dioxide, and benzaik〇nium chloride, sixteen a quaternary salt compound of cetyltrimethylammonium bromide and cetidipyridinium chloride. In other pharmaceutical compositions, one or more surfactants may be included to enhance physical stability or other specificity. Suitable nonionic surfactants include: polyoxyethylene fatty acid glyceride and vegetable oils such as polyoxyethylene (60) hydrogenated dry sesame oil; and polyoxyethylene alkylethers And Hyun • base phenyl shout, such as octyl gathering 10 (〇 ctoxynol 10), octyl condensed key 40. In still other compositions, one or more antioxidants may be included to increase the desired chemical stability. Suitable antioxidants include (for example only) ascorbic acid and sodium metabisulfite. In a particular embodiment, the pharmaceutical aqueous suspension composition is packaged in a single dose and non-repeatable opening container. Further, a multi-dose re-openable container may be used, where the composition generally contains a preservative. In another embodiment, a drug delivery system for a hydrophobic pharmaceutical compound can also be used. For example, the present invention may use a liposome and an emulsifier as a vehicle or carrier for administration. In a particular embodiment, an organic solvent such as N-decylpyrrolidone can be used. In still other embodiments, the compounds described herein can be administered using a sustained release system, such as a semipermeable matrix of a solid hydrophobic polymer containing a therapeutic agent. In addition, various sustained release materials can also be used in the present invention. In some embodiments, the sustained release capsule can release the compound over a period of hours, 67 201247612 or even over 24 hours. Additional protein stabilizers may be added depending on the chemical nature and biostability of the therapeutic agent. In a particular embodiment, the agents of the present invention may include one or more of an antioxidant, a metal chelating agent, a thiol containing compound, and/or other commonly used stabilizers. Examples of such stabilizers include, but are not limited to, (a) from about 0.5% to about 2% w/v glycerol, (b) from about 0.1% to about 1% w/v of methionine, ( c) from about 0.1% to about 2% w/v of monothioglycerol, (d) from about 1 mM to about 10 mM EDTA, (e) from about 0.01% to about 2% w/v of ascorbic acid, (f 0.003% to about 0.02% w/v of polysorbate 80 (p〇lysorbate 80), (g) 0.001. /. Up to about 0.05% w/v of polysorbate 20, (h) arginine, (1) heparin, (1) dextran sulfate, (k) cyclodextin, (1) pentose polysulfate and other heparinoids, (m) divalent cations such as magnesium ions and zinc ions; or (η) mixtures thereof. [Examples] Example 1: Demonstration of Preparation of Cyclohexenone Compounds Compound 1 (i.e., Antroq) was isolated from a solid-state fermenting mycelium of Antrodia camphorata by a conventional method (Lee, et al., Med, 73: 1412-1415, 2007). Based on previous research and experience, the effective dose of Compound 1 is 10-50 mg/kg body weight (Chang, et al.,

Comp/eweW d/iernai Med, 2008) ° Unless otherwise specified, the following experiments were conducted at a dose of 10-50 mg/kg body weight. 68 201247612 In addition, the exemplary compound 1 can be 4-hydroxy-2,3-dimethoxy-6-methyl-2,5-cyclohexane (4-hydroxy-2,3-dimethoxy-6-methyl-cyclo Prepared from hexa-2,5-dienone) or its analogs. Again, the other has

The cyclohexenone compound of the structure may also be obtained by isolating from Antrodia camphorata or by synthetic or semi-synthetic methods from a suitable starting material. Those skilled in the art will be able to employ appropriate conditions in the synthesis process. Example 2: Model establishment of localized glomerulosclerosis (FSGS) This experiment was conducted using an 8-week-old BALB/c female. FSGS mice were given intravenous adriamycin (0.1 mg/10 g body weight). Six hours before the doxorubicin injection, the mouse compound 1 was fed first. Here, the BALB/c female mice in which the physiological saline was intraperitoneally injected were used as the positive control group, and the ASLN mice fed the vehicle (corn oil) were used as the control group. Mice were sacrificed after 7, 14 or 21 days of disease induction, and spleens, renal cortical tissue, and blood samples were collected and appropriately preserved for subsequent analysis. All experiments were approved by the Animal Experimental Management Committee of the Taiwan National Defense Medical College and were based on laboratory animal care and NIH guidelines. Clinical and renal function assessment During the 3, 7, 14 and 21 days of feeding, urine samples were collected from the cage and tested for urine protein (Shui, et al., Ζ)ζ·α/ according to previously known methods. 2 1: 1 794-1 802, 2006). In addition, mice were sacrificed on day 7, 14 or 21 and mouse serum samples were collected to measure blood in the serum. 69 201247612 Blood urea nitrogen (BUN) and serum creatinine (creatinine,

The content of Cr). Renal lesion assessment Here, the use of formalin-fixed and paraffin-embedded kidney sections was used to assess the extent of kidney disease and kidney damage as described by Shui et al. (Shui, et al., 150: 216-222). , 2007). Renal lesions and renal damage scores were evaluated according to the method described by Shui. In addition, at least 50 kidney skeins of kidney tissue sections were taken to evaluate epithelial hyperplasia lesion (EPHL) and sclerosis. The number of glomeruli with EPHL is based on previously disclosed methods (for example, see Shui, et al., Nephrol Dial Transplant, 21: 1794-1802, 2006; Ka, et al, iVepAro/ Ζ) ζ α/ 21: 288-298, 2006), expressed as a percentage of the total number of kidney spheroids. In addition, immunohistochemistry (IHC) experiments were performed. Renal sections treated with formalin-fixed and paraffin-embedded, with primary antibody, biotinylated secondary antibody (Dako, Glostrup, Denmark), and avidin-biotin-peroxidase complex (avidin-biotin) -peroxidase complex) (Dako) reaction; the primary anti-system recognizes mouse interstitial protein (Desmin) (Lab Vision, CA, USA), CD3 (pan-T cell; Serotec, NC, USA), F4/80 (single) Nuclear leukocytes/macellus cells; Serotec), IL-6 (R&D Systems, MN, USA), NF-κΒ p65 (Cell Signaling Technology, MA, USA), serotypes I, III, and IV (Southern) Biotech, AL, USA), or TGF-pl (Santa Cruz Biotechnology, CA, USA) °

Example 3: Evaluation of ROS and NO 201247612 Here, according to conventional methods (Wu, et al., Α^ρΛγο/ D/a/Transplant, 2008, 23: 3082-3090, or Ka, et al., J Am. Soc. Nephrol. 2007, 18: 2473-2485) The in situ superoxide anion product of the kidney was detected by dihydroethidium (DHE) staining. Fluorescence images were measured to quantify the percentage of stained nuclei per cell kidney total cell nuclei. In addition, by conventional methods (Wu, et al., J Pineal Res, 2001, 30: 147-156, or Ka, et al., J. Am. Soc. Wep/iro/. 2007, 18: 2473-2485 ) Measurement of superoxide anion in serum and kidney tissue. The amount of ROS in serum, urine, and kidney tissues was measured by reacting the sample with a Krebs-HEPES buffer solution and using 1.25 mM lucigenin (Sigma.: - Aldrich Chemical Co, MO) as a substrate. The fluorescence count was measured by a known method using a Hidex Microplate Luminometer (Finland) (Kretzler, et al., F/rchowijrc/z, 425: 181-193, 1994). In addition, superoxide anion is expressed in terms of relative fluorescence units (RLU) per 15 minutes in weight per milligram of dry tissue, ie, RLU/15 minutes/mg or RLU/15 minutes/m. Bayer ij uses the NO test kit (iNtRON Biotechnology, Seongnam, Korea), which is expressed in terms of diazotization (Griess method) according to the manual. Example 4: Measurement of cellular GPx activity in kidneys A commercially available glutathione Peroxidase Assay kit (Cayman, MI, USA) and its manual were used to measure renal tissue. GPx activity. Here, the enzyme activity is expressed as a protein concentration relative to glomerular homogenates. 71 201247612 Example 5: Western blot analysis of Nrf2 and p47ph<) X The cytoplasm and nuclear protein in kidney tissue were extracted using a nuclear protein extraction kit (Active Motif, Tokyo, Japan) according to its manual. The target protein of the cytoplasm and/or nucleus in the kidney tissue was measured by western blot analysis using a rabbit antibody against mouse Nrf2 or p47ph°x (Santa Cruz). Here, the histone protein of the nuclear and cytoplasmic target proteins was measured using histone H3 (Cell Signaling, CO, USA) and β-actin (Santa Cruz) antibodies, respectively. Example 6: Measurement of TGF-pi Here, a commercially available ELISA kit (R&D Systems) was used, and the amount of TGF-βΙ protein in serum and kidney tissues was measured according to its manual. Here, the sample was acidified using I N HC1, and the acidified sample was neutralized using 1.2 N NaOH / 0.5 Μ HEPES to detect the amount of TGF-β prion protein. Example 7: AcP-IgAN model of B cell deficient mice B cell deficient mice (B6.129S2-Igh-6tmlCgn/J) were provided by the Institute of Molecular Biology, Academia Sinica (Prof. John T. Kung), and Animal Center of Taipei National Institute of Health, Taiwan. According to previous experiments (Chao, et al., 尤 叮 Λ / «Λ 70:283-297; 2006), through daily injection of purified IgA anti-battering test antibody and pneumococcal C-polysaccharide (pneumococcal Cp〇) Lysaccharide, PnC), to induce AcP-IgAN in mice. All experiments were approved by the Animal Experimental Management Committee of the Taiwan National Defense Medical College and were based on laboratory animal care and NIH guidelines. Clinical and pathological assessment 72 201247612 The body weight of mice was measured weekly. Urine samples from cages were collected weekly and urine samples were tested in samples according to previously known methods (Chao, et al., /πί. 70:283-297; 2006). Serum samples were collected on days 3 and 28 to measure the content of blood urea nitrogen (BUN) and serum creatinine (Cr) in Jinqing. 0 As for the histopathology of the kidney, the tissue was fixed with 10% formalin buffer and wrapped in paraffin. The sample was buried; then, hematoxylin and eosin staining (H&E) was used and the sections were stained (4 μιη). The proportion of renal spheroids with hyperplasia, crescent formation, sclerosis, or peri-glomerular inflammation in 50 random kidney spheroid samples was calculated under a light microscope at 400X magnification. Example 8: Immunofluorescence staining (IF), immunohistochemistry (IHC), and cell death assay. Frozen kidney tissue was treated according to the previous method and conjugated with fluorescein isothiocyanate (FITC). Goat anti-mouse IgA or C3 antibody reaction (Cappel, NC) for immunofluorescence staining. The staining intensity score is performed using a previously known method (Ch. Ao, et al., Ruler / «Λ 70:283-297 (2006)). Renal sections or cryosections of formalin-fixed and paraffin-embedded treatments, with anti-IL-6 (R&D Systems, MN, USA), MCP-1 (Santa Cruz, CA), F4/80 (mononuclear leukocytes/giant) Phage; Serotec, NC), collagen type I IV (Southern Biotech, AL), TGF_pi (Santa Cruz), squamized NF-k: B p65 (Cell Signaling, MA), CD3 (pan-T cell; Serotec CD4 (helper T cells; BioLegend, CA), CD8 (cytotoxic T cells), CD11b (macrophage/neutrophils), or CDllc (dendritic 73 201247612 cells) (BD Biosciences, CA) antibody The reaction was carried out for the IHC test. Next, the sections were reacted with FITC-co-consumed, AlexaFluor 488-common (Invitrogen, CA) or horseradish peroxidase (HRP) conjugated secondary antibody (DAKO, Denmark). Hematoxylin or 4,6-diamidino-2-phenylindole (DAK0) was used to calculate the stained nuclei. Apoptosis assays were performed with terminal deoxynucleotidyl transferase-related dUTP nick end labeling (TUNEL). The tissue of the formalin-fixed and paraffin-embedded tissues was sectioned and stained according to the manual using the ApopTag plus peroxidase in situ apoptosis detection kit (Chemicon, CA). The renal cortical area (including the renal pelvis and the peri-glomerular area) was measured and scored in a cell/kidney spheroidal section. Example 9: Flow cytometry The single-core nuclei (Splenocyte) of mice were treated with Tris buffered ammonium hydride. The red blood cells were removed and washed to contain 10% fetal bovine serum, HEPES buffer, L-branched tyrosine and penicillin. Resuspension of RPMI 1640 / streptomycin (both purchased from Invitrogen). Cells were stained with T or B cell activated surface markers. FITC·conjugated anti-mouse CD3, CD4, CD8, or CD19 (B cell) antibody and phycoerythrin (PE) conjugated anti-mouse CD69 antibody (both purchased from BD Biosciences) with FACSCalibur (BD Biosciences) ) for analysis. Example 10: T cell proliferation assay The single core of the mouse was treated according to the method described above, and then the cells were cultured in each well (200 μΐ/well containing 5 X 105 cells) in a 96-well flat-bottom microplate, and repeated three times. The microporous disc was first coated with 0.25 pg/ml of anti-mouse CD3 74 201247612 antibody (BD Biosciences) and allowed to stand overnight at 4 °C. At 48 hours, the cultured cells were treated with 1 μΟΜ of 3Η-methylthymidine deoxynucleotide (Amersham Pharmacia Biotech, NJ), collected after 16 hours, and measured for cell uptake using TopCount (Packard, PerkinElmer, MA). 3H-methyl thymus, bite deoxynucleotide. Example 11: Enzyme-linked immunosorbent assay (ELISA) for IL-Ιβ, IL-6, IL-18, and MCP-1 IL-1 P (eBi.osceience) was measured using a commercially available ELISA kit according to the instruction manual. , CA) 'IL-6 (eBiosceience) ' IL-18 (MBL, Japan) and MCP-l (eBiosceience). Nucleoproteins were extracted using a nuclear extraction kit (Active Motif, Japan). The Trans-AM ELIS A kit Trans-AM ELISA was used and the phosphorylated NF-κΒ p65 and renal cell nuclear factor-E2 correlation factor 2 (Nrf2) in renal tissue nuclear protein extracts were measured according to their manual. Renal cell proteins were extracted using RIPA buffer (Cell signaling). Cellular glutathione peroxidase (GPx) (Cayman, MI) and cell first hemoglobin oxidase (HO-1) (Enzo Life Sciences, NY)' were based on commercially available ELISA kits and their manuals. Make measurements. Both are expressed relative to the cell lysate protein concentration. Absorbance at 450 nm was measured using an ELISA reader (Bio-Tek, ΜΑ) in all ELISA assays. Example 12: Real-time PCR analysis

The total renal cortical RNA was obtained by extracting from the kidney cortex using TriZOL reagent (Invitrogen). For the first cDNA synthesis, the first reverse transcription reaction was performed using 1.5 pg of total RNA 75 201247612. Wherein, the reaction mixture comprises 0.9 pg of 12 to 18 unit oligo dT primer, 1.0 mM deoxyribonucleoside (dNTP), 1 pg of first buffer, 0.4 mM dithiothreitol, 80 U RNase complex ribonuclease inhibitor, and 300 U of super-transcription II RNase Η (Invitrogen). The real-time PCR was performed on an ABI Prism 7700 Sequence Debt Detector (ΑΒΙ Prism 7700 Sequence Detection System, Applied Biosystems, CA). All probes and primers are products of Assays-on-Demand Gene expression (Applied Biosystems). The real-time PCR reaction used a mixture of 10 μΐ of cDNA, 12.5 μM of TaqMan Universal PCR Master Mix (Applied Biosystems), and a special probe/primer of 1.25 μM in a total volume of 25 μM. The heating cycle was set at 50 ° C for 2 minutes, 95 ° C for 10 minutes, DNA separation for 40 cycles (95 ° C for 15 seconds), and then adhesion / extension reaction (60 ° C for 1 minute) Example 13: Western blot analysis Each protein sample was separated by 10% SDS-PAGE colloid. The colloidal electrotransfer was made into a polyvinylidene fluoride nitrocellulose membrane (Amersham Int., UK); fixed in blocking buffer (Tris-buffered physiological saline containing 5% skim milk) for 1 hour; and at 4 ° C And rabbit anti-nacht region-(nacht domain-), leucine-rich repeat-, and pyrin domain (PYD)-containing protein 3 (NLRP3), apoptosis Factor-1 (caspase-1) or β-actin antibodies (both purchased from Santa Cruz) were reacted overnight. After washing, the membrane was reacted with HRP-conjugated goat anti-mouse (DAKO) antibody for 1 hour at room temperature. A chemical luminescence reagent (chemiluminescent reagent plus, PerkinElmer Life Sciences, ΜΑ) was reacted with an antibody-bound membrane and measured by x-ray photography. 76 201247612 Example 14 :: Data Analysis Here, Student 1 s i test was used to perform data analysis comparison between the two groups, and the results were expressed as mean ± SEM. Among them, the differences between groups were analyzed by One-way Analysis of Variance (ANOVA) and Tukey's method was used for post-mortem analysis. Here, p < 0.05 indicates a statistically significant difference. The FSGS model in the disease control group, only vehicle-treated FSGS mice (FSGS control group), the amount of urinary protein increased significantly from day 7, and continued to increase until the 21st day of the end of the experiment. , as shown in Figure 1A. However, in the compound 1 treated FSGS mice (FSGS + Antroq mice), this phenomenon was significantly inhibited, and the increase in urine protein was similar to that in normal mice. In addition, compared with the control group FSGS mice, blood urea nitrogen (BUN) (Fig. 1B) and serum creatinine (Cr) were observed from day 14 to day 21 (Fig. 1C) The content was significantly and continuously increased; however, FSGS+Antroq mice (ie, Compound 1) had a significant increase in renal function. On day 7 of FSGS+Antroq mice, the amount of BUN or Cr was not significantly different from that of the control group (FSGS control group). In addition, histopathological examination of the renal pelvis section was performed at different time points (as shown in Fig. 2A). Compared with the normal control group of mice, in the FSGS control group, only the extracellular interstitial proliferation and aggregation of micro-renal spheroids were observed on the 7th day, and gradually increased from the 14th day to the 21st day. See obvious tissue damage. It is worth noting that from the 14th day to the 21st day, a significant and continuous increase in the proportion of mononuclear infiltration including EPHL and renal spheroids was observed, which represents the pathological state of 77 201247612. In contrast, in FSGS+Antroq mice, these progressive renal failures were significantly reduced. In addition, the podocyte injury and disappearance is a pathological marker that can determine whether FSGS is developing. In order to examine the changes in the expression of Antroq-treated FSGS podocytes, the expression of interstitial protein (Desmin) was examined using tissue immunostaining, which is a marker for identifying podocytes. As shown in Fig. 2B, on day 14 and day 21, the intermuscular protein expression of FSGS+Antroq mice was significantly inhibited significantly compared to the FSGS control group, even in the normal control group. Some phenomena of micro-muscle protein expression can be observed. These results show that the exemplified compound 1 inhibits an increase in urinary protein, enhances renal function, improves renal failure including endothelial proliferative failure (EPHL), and improves renal pelvic damage. The effect of systemic inhibition of oxidative stress in serum and urine compared with the normal control group of mice, in the FSGS control group (FSGS + vehicle), the amount of superoxide anion in serum was evident on days 7 and 14. Increased, but decreased slightly on day 21, but still slightly higher than the normal control group of mice. However, when Example Compound 1 (Antroq) was administered from Day 7 to Day 21, the production of superoxide anion was effectively adjusted, and the amount of superoxide anion was similar to that of the normal control group, as shown in Fig. 3A. In addition, in the FSGS control group, the amount of NO in the serum increased significantly on the 7th day, and a high concentration was observed on the 14th day and the 21st day. When FSGS mouse exemplified compound 1 (FSGS + Antroq) was administered, a high serum NO amount was significantly inhibited as shown in Fig. 3B. A significant increase in the amount of superoxide anion in the urine was observed on day 7 compared to the normal group of mice in the FSGS control group and maintained to the ground 21 78 201247612 days. On the contrary, in the FSGS + Antroq mice, when the exemplified compound 1 was administered, the amount of superoxide anion was remarkably lowered as shown in Fig. 3C. Although the amount of NO in the urine of the FSGS-controlled group was significantly increased from day 14 to day 21, administration of the exemplified compound 1 attenuated this phenomenon in FSGS+Antroq mice, as shown in Fig. 3D. On day 7, no significant difference in the amount of NO in the urine of the normal control group, FSGS+ carrier, and FSGS+Antroq mice was observed. Local inhibition of ROS production in kidney tissue As shown in Figure 3E, the amount of superoxide anion in the kidneys of the FSGS control group was observed to increase significantly on day 14 compared to the normal control group, and continued to increase to Day 21 However, from day 14 to day 21, it was observed that administration of Antroq effectively regulated the production of superoxide anion, and the amount of superoxide anion was similar to that of the normal control group. To better understand the location of ROS in the renal pelvis, the in situ ROS product of kidney tissue was measured using the dihydrogen ingot (DHE) assay. As shown in Fig. 3F, in the kidney tissues of the mice in the FSGS control group, the amount of DHE fluorescence increased from day 14 to day 21, especially in the renal glomeruli and renal tubules, indicating that compared with Normal group mice had in situ ROS production. On the other hand, on day 14 to day 21, only a very small amount of DHE fluorescence was observed in FSGS+Antroq mice.

The Nrf-2-associated antioxidant signaling pathway is used to measure the expression of NAD(P)H oxidase unit p47phux in the kidney, Nrf2 transfer to the nucleus (activation), and GPx activity to understand Antroq's pathway in the antioxidant signaling pathway. efficacy. 79 201247612 In the air, from the 14th day to the first

As shown in Figures 4A and 4C, FSGS control group / sputum, stomach 21 days 'can observe a significant increase in NAD (P) H oxidase, while administration of Antroq can inhibit FSGS normal group mice or normal mice, mice The transfer of the 2nd to the nuclear condition was significantly increased, and (4) was maintained until the 21st day, as shown in Figures 4B and 4D. Further, as shown in Fig. 4E, the GPx activity of the mice in the control group was significantly decreased as compared with the mice in the normal control group, and the GPx system was one of the downstream phase II enzymes of Nrf2. However, compared with the FSGS control group, GPGS activity was restored in the FSGS+Antr〇q mice on day 7, and the same situation was observed until the 21st day when the mice were sacrificed. This result shows that the exemplified compound 1 can inhibit ROS/NO production, but increases Nrf2 activation and GPx activity. T cell and macrophage infiltration The interstitial recruitment of macrophages and lymphocytes is one of the factors that evaluate FSGS inflammation and fifi (Profibrotic). Here, the effect of the exemplified compound 1 on renal tissue T cells and/or mononuclear leukocyte/macrophage infiltration was evaluated. In the FSGS control group, on day 14 and day 21, significant T cells (CD3+) and mononuclear leukocytes/macrophages (F4/80+) were found in the renal spheroidal region between kidney tissues. Infiltration phenomenon, but FSGS+Antroq mice were similar to the normal control group, and no significant infiltration was observed, as shown by circles 5A and 5B. IL-6 Performance 201247612 Here, IL-6 production in the kidney is measured. As shown by the IHC results in Figure 6A, a significant increase in IL-6 protein expression was observed on day 7 and continued to rise until the 21st day of sacrifice. However, the expression of IL-6 protein in the kidney of FSGS+Antroq mice was significantly lower than that of the FSGS control group mice. Inhibition of NF-κΒ activity Here, the administration of exemplary compound 1 to kidney tissue NF- was measured. The effect of κΒ activity. As shown in Fig. 6B, the nuclear NF-κΒ p65 expression of the FSGS-controlled mice was significantly increased on the 14th day and the 21st day, while the NF-κΒ activity of the FSGS+Antroq mice was significantly inhibited. Consistent with the results of the IHC experiment, the ELI SA test of the nucleoprotein extract of renal pelvis also showed that NF-κΒ p65 nucleoprotein expression was observed on the 14th day in the FSGS control group compared with the normal control group. Increased and still increased significantly on day 21. However, this phenomenon of FSGS + Antroq mice was slightly inhibited when the compound 1 (Antroq) was administered on the 14th day, and was significantly inhibited on the 21st day. In addition, on day 7, it was observed that there was a significant difference between the FSGS control group or the FSGS+Antroq mice, as shown in Fig. 6C. Therefore, when the cyclohexenone compound of the present invention is administered, the activation of NF-κΒ in the kidney can be inhibited, and the inflammatory reaction can be effectively inhibited. In addition, the FSGS model was also observed to observe the protein expression of fibrosis, namely collagen I, III and IV, in order to understand the effect of administration of the cyclohexenone compound on renal fibrosis. As shown in Figures 7A-7C, kidney collagen I and IV were observed from day 14 to day 21 in the FSGS control group compared to the normal control group. Collagen 81 was observed on day 21. 201247612 Protein III; while administration of Compound 1 significantly inhibited the production of such proteins, and the amount of expression in FSGS+Antroq mice was not significantly different from that in the normal control group. TGF-β Ι is one of the basic growth factors and growth hormones of renal fibrosis and crescentic formation. ELIS A results show that serum can be observed on day 14 in FSGS mice compared with normal control mice. The amount of TGF-pl protein was increased in the middle (Fig. 8A) and in the kidney tissues (Fig. 8B), and was significantly increased on the 21st day. However, when the exemplified compound 1 was administered, the amount of the increased TGF-β prion protein was inhibited regardless of the serum or the kidney. Here, the change in the amount of TGF-βΙ protein expression in the renal tissues was determined by the IHC test. Similarly, IHC results showed that the amount of TGF-βΙ protein in the kidneys of FSGS+Antroq mice was significantly lower than that in the FSGS control group, as shown in Figure 8C. Therefore, when the cyclohexenone compound provided by the present invention is used, the expression of TGF-βΙ protein can be effectively inhibited, and it can be applied to the treatment of glomerular sclerosis.

The IgAN model was administered with AcP-IgAN mice (AcP-IgAN control group mice) as a disease control group, which increased the amount of urinary protein on the 7th day of the induced disease and continued until the 28th day after the end of the experiment. Rise, as shown by circle 9. However, AcP-IgAN mice (AcP-IgAN + Antroq mice) treated with Compound 1 were greatly inhibited, although some micro-urinary protein production was observed compared to the normal control group. . In addition, the AcP-IgAN control group had a significant increase in BUN serotype (Fig. 9B) and serum creatinine (Fig. 9C) on day 28; although AcP-IgAN+Antroq mice and AcP-IgAN control group, normal Group mice did not have significant differences in BUN and Cr serum levels on day 3, but AcP-IgAN+Antroq mice showed better renal function. 82 201247612 The growth of the mice in the eAcP-IgAN+Antroq mice and the AcP-IgAN control group mice was measured weekly, which was no different from the normal control group. In addition, all mice in each group exhibited normal activity without a change in hair loss or appetite. Renal pathology tests are shown in Figures 9A-9E. On day 28, mice in the AcP-IgAN control group had neutrophil infiltration, local but typical crescent, and/or spheroidal segmental sclerosis. Correlation of increased infiltration, and significant renal mononuclear leukocyte infiltration and scattered tubular atrophy (related to protein shedding), this result shows that compared with the previous study of renal spheroid tissue pathology report (Lai, KN Nephron. 92:263-270 (2002) ; Lai, et al., Nephron. 69:1-8 (1995); Chen, et al., J. Clin. Lab. Analysis. 6:35-39 (1992) Kashem, et al". /«ί· 45: 868-875 (1994)), and histopathological study of the renal interstitial (Falk, et al., along the curry/«ί. 47:177-185 (1995) Van Es, et al., Kidney Int. 73:1426-1433 (2008); Torres, et al., Kidney Int. 73:327-333 (2008); Walsh, et al., Clin J Am Soc. Nephrol 5: 425-430 (2010); Fujinaka, et al., J. #ep;7rc)/· 20:357-363 (2007)), with an increased and worsened state of kidney disease, except for renal glomerular immunoprecipitation All other kidney damage in AcP-IgAN+Antroq mice, other than kidney damage All of them were inhibited. On the third day, the control group AcP-IgAN mice began to have localized nephropathy, but the renal histopathology of AcP-IgAN+Antroq mice treated with Compound 1 was again significantly inhibited. Renal DNA-related genes and protein expression 83 201247612 Here, the mRNA and protein expressions of TGF-βΙ and Co丨-IV in mice were detected. Although the AcP-IgAN control group mice were smaller than the normal control group. In mice, the mRNA expression of TGF-βΙ and Col-IV increased significantly on the 28th day, but in the AcP-IgAN+Antroq mice administered Compound 1, this phenomenon was greatly inhibited, as shown in Figures 10A-10D. On the third day, only two groups of mice observed the underlying mRNA expression of the basal bright fibrosis-related genes. Conversely, on day 28, the IHC results showed that the AcP-IgAN control group mice The amount of protein of TGF-βΙ and Col-IV was greatly increased, but this phenomenon was significantly inhibited in AcP-IgAN+Antroq mice. Cellular Immunity and Renal Inflammation Here, cell-associated immune phenomena are observed by IgAN pathology experiments. Flow cytometry experiments with splenocytes were performed to detect CD3, CD4 and CD8 activities, respectively. As shown in Figures 11A-11C, on day 3, a significant increase in the percentage of CD3+/CD69+, CD4+/CD69+ or CD8+/CD69+ was observed in the AcP-IgAN control group compared to the normal control group. However, no similar situation occurred in all subtypes of T cells on day 28. Conversely, on day 3, treatment with Compound 1 induced a significant decrease in the percentage of CD3+/CD69+ T cells in AcP-IgAN+Antroq mice compared to AcP-IgAN control group mice. However, on day 3, there was no significant difference in the percentage of CD4+/CD69+ or CD8+/CD69+ T cells between AcP-IgAN control group mice and AcP-IgAN+Antroq mice. In the normal control group, the percentage of each of the three T cells was not different on the 28th day. The results of thymidine uptake analysis showed that on day 3, CD3+ T cells in the spleen 84 201247612 spleen cells of the AcP-IgAN control group were significantly more proliferating than AcP-IgAN+Antroq mice (Fig. 11A-11C), and on day 28, the baseline values of proliferation in each group of mice were similar to those in the normal control group. In addition, mononuclear white blood cell performance infiltrated in the kidneys of the mice was also assessed by the IHC test. As shown in Figures 12A-12F, AcP-IgAN mice observed only a small amount of inflammatory cells in the kidney on day 3, but on the 28th day, in the renal interstitial. Local but significant CD4+ Th cells, CD8+ Tc cells, CDllc+ phagocytic leukocytes, F4/80+ monocytes/macrophages, and CD11b+monocytes/macrophage cells were observed in the tissues. In Acp_igAN mice, the inflammatory cell infiltration of the kidneys of AcP-IgAN+Antroq mice was significantly reduced on day 28, and on day 3, the kidneys of AcP-IgAN+Antroq mice were almost unable to detect pan-T. Signals for cells, sputum neutrophils, and mononuclear leukocytes/macrophages. Oxidative stress, Nrf2, and related pathways ROS is one of the major harmful chemical mediators for determining the acceleration or worsening of various forms of kidney disease, including igAN. The amount of ROS expression can be systematically detected in the blood and the amount of ROS expression can be observed locally in the kidney tissue. Compared with the normal control group, AcP-IgAN mice showed a significant increase in serum ROS on day 3 and day 28, while in urine and kidney tissues, ROS was observed on day 28 The amount increase is as shown in Figures 13A-13F. In contrast, AcP-IgAN+Antroq mice administered the exemplified compound 1 of the present invention had a large decrease in the amount of R〇S in the serum on day 3 as compared with the AcP-IgAN control group mice. On day 28, the amount of r〇s in serum, urine and kidney tissue was also greatly reduced. In addition, on day 3 until day 28, the amount of urinary nitric oxide (NO) in the AcP-IgAN control 85 201247612 group was higher than that in the normal control group. However, a significant decrease in NO was observed on days 3 and 28 of AcP-IgAN + Antroq mice compared to AcP-IgAN control mice. Although there was no significant difference in the amount of NO in serum between AcP-IgAN control group and AcP-IgAN+Antroq mice on day 3, at day 28, the amount of NO in the serum of AcP-IgAN+Antroq mice was higher than that of AcP. -IgAN mice were substantially reduced. Next, the exemplified compound 1 of the present invention will be administered to observe the possible mechanism for causing the above results, as shown in Figs. 14A to 14F, from the third day to the 28th day of the sacrifice of the mouse, compared to AcP-IgAN. The mRNA and protein base expression of Nrf2 in the control group mice, and the mRNA and protein expression of Nrf2 in AcP-IgAN+Antroq mice were greatly increased. In addition, the glutathione peroxidase (GPx) of the downstream protein of Nrf2, on day 28, the expression level in the kidney tissue of AcP-IgAN+Antroq mice was significantly higher than that in the AcP-IgAN control group, although There was no significant difference between the two groups of mice on day 3. Amount of serum proinflammatory cytokines First, as shown by circle 15B, the amount of serum MCP-1 was significantly increased in the AcP-IgAN control group on day 3, and this phenomenon continued until the 28th day of mouse sacrifice. In contrast, in AcP-IgAN + Antroq mice, this phenomenon was greatly suppressed and was similar to the basal amount. In addition, although there was no significant difference in serum IL-6 levels between AcP-IgAN control group mice, AcP-IgAN+Antroq mice, and normal control group mice on day 3, on day 28, 'AcP-IgAN+ The amount of serum IL-6 in Antroq mice was significantly decreased (as shown in Figure 15A), while the serum IL-6 levels in the AcP-IgAN control group were significantly higher than those in the normal control group. On day 28, the amount of serum IL-Ιβ in the 86 201247612 mice in the AcP-IgAN control group was significantly higher than that in the normal control group, but this phenomenon was significantly inhibited in AcP-IgAN+Antroq mice (Fig. 15C). Shown). On day 3, no more normal control group mice were observed in the AcP-IgAN control group mice and the 11^-18 doses of the gossip--4 八1<1+6111^〇9 mice. There is an increase phenomenon as shown in Fig. 15D. Although the amount of serum IL-18 in the AcP-IgAN control group and AcP-IgAN+Antroq mice increased almost the same on day 3 compared to the normal control group, on day 28, AcP-IgAN Serum IL-18 levels in control mice were significantly increased, whereas in AcP-IgAN + Antroq mice, serum IL-18 levels were inhibited. NLRP3 inflammatory 逋 activation (in the kidney) NACHT, LRR and PYD region protein 3 (NALP3) inflammatory sputum is highly correlated with inflammatory response and is associated with adaptive immunity" although NLRP3 is associated with subjective and pathological changes Intermolecular relationships have been confirmed, but its relationship with immune complex-associated renal glomerular disease remains unclear. "Whether NALP3 inflammatory activation will occur in AcP-IgAN mice, AcP-: [gAN mouse model Established, still associated with increased local inflammation of the kidney. On day 3 and day 28, although AcP-IgAN mice had a significant increase in NLRP3 protein in the renal pelvis of the normal control group, this phenomenon was significantly inhibited in AcP-IgAN + Antroq mice. In the AcP-IgAN control group and AcP-IgAN+Antroq mice, the mRNA expression of NLRP3 was higher than that in the normal control group, but compound 1 was not administered to NLRP3 of AcP-IgAN+Antroq mice. mRNA performance has an effect. However, on day 28, the mRNA expression of NLRP3 in the kidney of AcP-IgAN+Antroq mice was significantly lower than that in the AcP-IgAN control group, 87 87476612

The renal niRNA expression of this gene in the AcP-IgAN control group mice was still much higher than that in the normal control group. Importantly, from day 3 to day 28, quantitative real-time PCR analysis showed that the mRNA expression levels of apoptotic factor-1 and IL-18 in AcP-IgAN+Antroq mice increased significantly, but this The risk was inhibited in AcP-IgAN+Antroq mice, as shown in Figures 16A-16F. In addition, on days 3 and 28, Antroq's AcP-IgAN was administered compared to the AcP-IgAN control group. The renal apoptotic factor-1 protein expression was inhibited in +Antroq mice, although the renal IL-18 protein production line of AcP-IgAN+Antroq mice was significantly inhibited on day 28. On day 28, the mRNA expression of IL-Ιβ in the AcP-IgAN control group was significantly increased, but it was significantly inhibited in AcP-IgAN+Antroq mice, although it was not observed on the third day. The mRNA expression of IL-Ιβ in the kidney increased. Renal NF-κΒ activation and related cytokines Based on the apparent mononuclear leukocyte infiltration in the kidneys of AcP-IgAN mice, local inflammatory response in the renal pelvis appears to be the main pathway for IgAN acceleration and progression. Here, we study the role of NF-κΒ in the kidney. First, as shown in Figures 17A-17F, compared to the AcP-IgAN control group mice (the amount of nuclear NF-κΒ protein in the kidney was significantly increased on day 28 compared with the normal control group), AcP-IgAN+Antrqo was small. The nuclear NF-kB protein expression in the rat kidney was significantly reduced, although on day 3, both the AcP-IgAN control group or the AcP-IgAN+Antrqo mouse had a normal expression of the protein in the kidney. The mice in the group did not differ much. In addition, the IHC results from kidney tissue on day 28 showed a significant increase in nuclear transfer compared to the AcP-IgAN control group. Compound 1 was more able to significantly reduce NF-κ nucleus 88 in AcP-IgAN+Antrqo mice. 201247612 The effect of the transfer. In addition, quantitative analysis of mRNA and protein expression of MCP-1 (Fig. 17C) and IL-6 (Fig. 17D) in the kidneys was performed. Although the AcP-AgNA control group mice, AcP-IgAN+Antrqo mice and the normal control group mice did not differ significantly on the third day, on the 28th day, compared with the AcP-IgAN control group mice, Administration of Compound 1 significantly reduced the mRNA and protein expression of MCP-1 and IL-6 in the kidney of AcP-IgAN+Antrqo mice, as shown in Figures 17E and 17F. Apoptosis in the kidney The apoptosis test in the kidney is used to understand the pathology of IgAN. As shown in Fig. 18-188, the results of 1'13\5 1^ showed that the apoptosis of the control group at the 28th day was significantly higher than that of the normal control group. However, this phenomenon was significantly inhibited in AcP-IgAN+Antroq mice administered to Antroq; even on day 3, apoptosis was not observed in all mice. Example 15: Parenteral dosage form A pharmaceutical composition suitable for parenteral injection administration is prepared by dissolving 100 mg of the compound of the present invention or a salt thereof in dmsO, followed by 0.9% sterility with 10 mL. Mix saline when physiological. The mixture is then packaged in a pharmaceutical unit suitable for injectable administration. Example 16: Oral dosage form A pharmaceutical composition for oral administration was prepared by mixing 1 mg of the exemplary compound 1 with 1 mg of corn oil. The mixture is then packaged in an oral unit, such as a capsule, for oral administration. 89 201247612 In some embodiments, 100 mg of the compound of the invention is mixed with 750 mg of starch and the mixture is packaged in an oral unit, such as a hard gelatin capsule, for oral administration. Example 17: Sublingual Administration (Hard Tablets) Formulations A pharmaceutical composition for buccal administration, such as a hard tablet dosage form, is prepared by mixing 100 mg of a compound of the invention with 420 mg of sugar powder, and Mix 1.6 mL of light corn syrup, 2.4 mL distilled water, and 0.42 mL of peppermint extract. Thereafter, the mixture is carefully ground and the ground mixture is poured into a mold to form a lozenge suitable for buccal administration = Example 18: Inhalation Composition Preparation of a pharmaceutical composition for inhalation administration, system 20 The compound of the invention of mg is mixed with 50 mg of anhydrous citric acid and 100 mL of a 0.9% sodium hydride solution. The mixture is then packaged in an inhalation dosing unit, such as a spray gas, for inhaled administration. Example 19: Rectal Gel Formulation A pharmaceutical composition for rectal administration is prepared by applying 100 mg of the compound of the present invention to 2.5 g of methylcellulose (1500 mPa), 100 mg of methylparabenzate. (methylparapen), 5 g of glycerin, and 100 mL of pure water. The gel mixture obtained will then be packaged in a continuous enteral administration unit, such as a syringe, for rectal administration. Example 20: Topical gel composition

Preparation of a topical gel pharmaceutical composition comprising 100 mg of a compound of the invention with 1.75 g of hydroxypropylcellulose, 10 mL of propylene glycol, 10 mL of isopropyl myristate, And 100 mL of USP 90 201247612 grade ethanol. The gel mixture thus prepared is then packaged in a container, such as a hose, for administration in a suitable manner. Example 21: Eye Drop Composition The eyedrop composition error was prepared by mixing 100 mg of the compound of the present invention with 〇.9 g of Nac丨 (dissolved in 100 mL of pure water) and using 〇2 μm. The filter membrane was filtered. The resulting non-ionic solution is then packaged in an ocular administration unit, such as an eye drop container, for application to the eye. <Desc/Clms Page number>> These examples are understood to be illustrative only. Various changes, modifications, and substitutions can be made by those skilled in the art without departing from the scope of the invention. In addition, various changes to the embodiments of the invention are to be construed as the invention. At the same time, the scope of the claims of the present invention is intended to be within the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS The features of the present invention are as set forth in the claims. The embodiments of the present invention are set forth to provide a better understanding of the features and advantages of the present invention. Figure 1A-1C is a study of the inhibition of urinary protein and the improvement of renal function by a cyclohexenone compound. (Fig. 1A) Study of urine protein over time; (Fig. 1B) Blood/month blood urea Gas (BUN) content; (Figure ic) serum creatinine amount, wherein, 201247612 These data are expressed by the mean SEM of each group of 6 mice, wherein *;?&lt; 0.05, ** /?&lt;0.01, ***/?&lt;0.005,#Unable to measure. 2A-2B are the results of inhibition of renal histopathological development of the exemplified compound 1: (Fig. 2A) H&E staining renal histopathological evaluation on days 7, 14, and 21 of administration; (Fig. 2B) on administration of drugs 7, 4 Tissue immunostaining of 21-day intermuscular line protein was used to measure the cerebral injury of the glomerulus of the kidney; the front of the black arrow, the front end of the white arrow, and the arrow indicate epithelial hyperplasia (EPHL), sclerosis, and podocytes, respectively; The magnification was 400X, and the semi-quantitative analysis was shown on the right side of the circle. These data were expressed as the mean SEM of each group of 6 mice, of which corpse &lt; 0.05, **/?&lt; 0.01, * **/?&lt;0.005,# cannot be detected. 3A-3F are the results of exemplified compound 1 to protect FSGS mice from ROS/NO: (Fig. 3A) the amount of superoxide anion in serum; (Fig. 3B) the amount of NO in serum; (Fig. 3C) the amount of superoxide anion in urine; (Fig. 3D) The amount of NO in the urine; (Fig. 3E) The amount of superoxide anion in the kidney protein; (Fig. 3F) The in situ ROS production of the kidney calibrated with dihydrogen ingot (DHE); the initial magnification is 400X, semi-quantitative analysis shows On the right side of the figure, these data are expressed as the mean SEM of the experimental results obtained for each group of 6 mice, where *p &lt; 0.05, ** household &lt; 0.01, *** /? &lt; 0.005. 4A-4E are the results of the enhanced nuclear Nrf2 expression of the exemplified compound 1 and the inhibition of intracellular P47ph°x protein expression: (Fig. 4A) and (Fig. 4B) are the intracellular p47ph°x and the west of Nrf2 in the kidney tissue, respectively. Ink dot test results, in which β-actin and histone Η3 lines were used as intracellular and nuclear protein control groups, respectively; (Fig. 4C) ρ47ρΗ°χ/β-actin ratio quantified values; (Fig. 4D) Nrf2 /Histone H3 ratio quantified values; (Fig. 4E) GPx activity in the kidney; these data are expressed as SEM of the experimental mean of each of 6 mice in each group of 92 201247612, of which 0.05 ' **p&lt; o. Oi. ***p&lt;〇.〇〇5 〇 Figure 5 A - 5 Β is a sample compound 丨 τ cell and macrophage infiltration results: (Figure 5 Α) measured by tissue immunostaining CD3 + τ cell results; (Fig. 5B) The F4/8 〇 mononuclear leukocyte/macrophage results were measured by tissue immunostaining with an initial magnification of 4 〇〇χ, the red arrow shows CD3+ τ cells, and the half sputum analysis is shown on the right side of the figure. These data are obtained by the average of the experiments obtained for each group of 6 mice: fcSEM, where 〇. 〇5, **p&lt; 〇〇1, ***;?&lt;0.005 » Round 6A-6C is the result of inhibition of IL-6 expression activity in the kidney by the example compound j: (Fig. 6A) measured by tissue immunostaining Jiang_6 protein; (circle 6B) measured by tissue immunostaining measurement of ΝΙγ·κΒ p65, where the initial magnification is 400X, semi-quantitative analysis is shown on the right side of the figure; (Fig. 6C) activity; The experimental mean SEM obtained for 6 mice indicates 'where 〇.05, *&gt;&lt; 〇〇 1, (8) 5. 7A-7C are the results of exemplifying the inhibition of collagen egg ΑΙ πι &amp;ιν aggregation in the kidney: (Fig. 7Α) detecting collagen 1 by immunohistochemical staining; (Fig. 7Β) detecting collagen 111 by immunohistochemical staining; (Fig. 7C) Collagen IV was detected by immunohistochemical staining; the initial magnification was 4 〇〇χ, and the semi-quantitative analysis is shown on the right side of the figure. These data are the mean values of the experiments obtained for each group of 6 mice. SEM indicates that **ρ&lt; 〇.〇1. 8A-8C are the results of inhibiting the expression of TGF-βΙ in serum and kidney tissues of exemplary compound 1: (Fig. 8Α) detecting the amount of TGF-βΙ in serum by immunohistochemical staining; (Fig. 8Β) staining with immune tissue staining In the renal protein, the amount of ^93 201247612 was measured; (Fig. 8C) TGF-β 1 was detected by immunohistochemical staining; the initial magnification was 400X, and the semi-quantitative analysis was shown on the right side of the figure. These data were 6 mice per group. The experimental mean soil SEM obtained is represented by 0.01, ***p &lt; 〇.005. 9A-9E are diagrams showing the reduction of urinary protein and elevation of renal function in AcP-IgAN mice by the cyclohexenone compound 1 and as a result of pathological sectioning of kidney tissue: (Fig. 9A) Study of urine protein changes over time; 9B) blood urea nitrogen (BUN) content in serum; (Fig. 9C) serum creatinine amount; (circle 9D) after treatment on day 3 and day 28 'assessment of renal histopathology by h&e staining; (Fig. 9e After treatment on the 3rd day and the 28th day, the histopathology of the kidney was evaluated by PAS staining; the initial magnification was 400X, and the affected spheroid percentage was below the figure. These data were 6 small each group. The experimental mean ± SEM obtained by the mouse indicates that *p &lt; 0.05, **p &lt; 0.01, 〇〇5, # could not be tested. Round 10A-10D is the result of mRNA and protein expression of TGF-βΐ and Col-IV when feeding Acp_igAN mice with the example cycloheximide compound 1; (circle 10A) to detect TGF-β in the kidney by real-time PCR Results of mRNA expression; (Fig. 10B) Results of mRNA expression of collagen I in the kidney by real-time PCR; (Fig. 10C) Results of protein expression of TGF-β in the kidney by immunohistochemical staining; 10D) The results of protein expression of collagen I in the kidney were detected by immunohistochemical staining; the initial magnification of 400X' is shown below the figure, and the data are the average of the experiments obtained for each group of 6 mice. SEM said that **;?&lt; 〇.(H, ***p&lt;〇.〇〇5. 94 201247612 Figure 1 ΙΑ-11C is a cell for detecting IgAN pathology in spleen cells by flow cytometry Results of related immune responses: (Fig. 11A) Percentage of CD3+CD69+ cells in CD3+ spleen cells after treatment on day 3 and day 28; (circle 11B) CD19+ spleen cells in CD19+ spleen cells after treatment on day 3 and day 28 +CD69+ cell percentage; (Fig. 11C) T cell proliferation results; such data are per The experimental mean SEM of each of the 6 mice was expressed, where */?&lt; 〇.〇5, **p&lt;0.01, **&gt;&lt;〇.〇〇5,# could not be detected. The 12A-12F line was evaluated for the type of mononuclear platinum cell immersion in the kidney of AcP-IgAN mice: (圊12A) to measure CD3 + T cell results by immunofluorescence staining; (Fig. 12B) to immunofluorescence Staining measures CD4+ T cell results; (Fig. 12C) CD8+ T cell results were measured by immunofluorescence staining; (Fig. 12d) CD1 lb macrophage/phagocytic leukocyte results were measured by immunohistochemical staining; (Fig. 12E) immunization Tissue staining was used to measure CD1 lc dendritic cell results; (Fig. 12F) F4/80 monocyte/macrophage results were measured by immunohistochemical staining; initial magnification was 400X, numerical series are below the graph, and these data are in each group. The experimental mean ± SEM obtained for each of the 6 mice, wherein *p &lt; 0.05, **/&gt;&lt; 0.01, ***; ? &lt; 〇.〇〇5, # could not be detected. -13F is an example of cycloheximide compound 1 inhibiting ROS/NO production in AcP-IgAN mice: (Fig. 13A) Superoxide anion in serum; (Fig. 1 3B) the amount of NO in the serum; (Fig. 13C) the amount of superanion in the urine; (Fig. 13D) the amount of NO in the urine; (Fig. 13E) the amount of superoxide anion in the kidney; (Fig. 13F) in dihydroethylene ingot (DHE) The stained kidney in situ R〇s produced a side-detection result; the initial magnification was 400X 'the numerical series is on the right side of the figure, and the data is in each group.

95 201247612 The mean value of the experiment obtained by each of the 6 mice is ± SEm, where *p &lt; 0.05, **p &lt; 0.01, ***p &lt; 〇.〇〇5. Figures 14A-14F are the results of mRNA and protein expression of Nrf2 in AcP-IgAN mice: (Fig. 14A) Results of mRNA measurement of renal Nrf2 by real-time PCR; (圏14B) Measurement of mRNA of kidney NQ01 by real-time PCR The result of the amount; (Fig. 14C) the result of measuring the amount of mRNA of kidney HO-1 by real-time PCR; (Fig. 14D) the result of measuring the amount of nuclear ΝγΠ in the kidney by ELISA; (Fig. 14Ε) measuring the cell ΗΟ-1 in the kidney by ELISA Results of performance; (14F) GPx activity results in kidneys; these data are expressed as SEM of experimental mean values obtained from 6 mice per group, where *p&lt; 0.05, **/?&lt; 0.01, *** Corpse &lt;〇.〇〇5. Figures 15A-15D are measurements of serum inflammatory factor levels in AcP-IgAN mice; (Figure 15A) IL-6; (Figure 15B) MCP-1; (Figure 15C) IL-Ιβ; (Figure 15D) IL- 18; such data are expressed as SEM of the experimental mean values obtained for each group of 6 mice, wherein * corpse &lt; 0.05, **p &lt; 0.01, ***; ? &lt; 〇.〇〇5.囷16A-16F is a measure of renal NLRP3 inflammatory body activation in AcP-IgAN mice: (Fig. 16A) Measurement of renal NLRP mRNA expression by real-time PCR; (Fig. 16B) Measurement of renal apoptosis factor-1 by real-time PCR mRNA expression level; (Fig. 16C) mRNA expression of renal IL-Ιβ was measured by real-time PCR; (Fig. 16D) mRNA expression of renal IL-18 was measured by real-time PCR; (Fig. 16E) NLRP3 western ink in kidney tissue Point test results; (Fig. 16F) Western blot test results of apoptotic factor-1 (Casp 1) in kidney tissue; among them, Caspl p20 subunit appeared to represent activation, β-actin as internal control histone, 0 · 05, 0·01, ***ρ&lt;〇·〇〇5. 96 201247612 Figures 17A-17F are examples of inhibition of IL-6 and MCP-1 expression in the kidneys of AcP-IgAN mice by a cyclohexenone compound 1 and an increase in NF-κΒ activation: (Fig. 17A) Measurement of NF by tissue immunostaining The result of -κΒ p65, where the initial magnification was 400X, and the numerical series is below the figure; (Fig. 17B) the result of measuring NF-κΒ in the kidney using the ELISA-based TransAM NF-κΒ set; (Fig. 17C) measuring the kidney by real-time PCR The result of the amount of mRNA of MCP-1; (Fig. 17D) the result of measuring the mRNA amount of renal IL-6 by real-time PCR; (Fig. 17E) the result of measuring the protein amount of renal MCP-1 by tissue immunostaining; (Fig. 17F) The results of tissue immunostaining were used to measure the protein content of renal IL-6; the initial magnification was 400X, and the numerical series are shown below. These data are expressed by the mean SEM of the experimental results obtained from each group of 6 mice. Where */7&lt; 0.05, **/?&lt; 0.01, ***;?&lt;〇.01)5. Figures 18A-18B are the results of apoptosis assays in the kidneys of AcP-IgAN mice: (Fig. 18A) Measurement of apoptosis in the kidney by terminal deoxynucleotidyl transferase-related dUTP nick end labeling (TUNEL) As a result, the initial magnification was 400X; (Fig. 18B) the number of cells having apoptosis in the kidney; these data were expressed by the mean SEM of the experimental results obtained from 6 mice in each group, where */? &lt; 0.05, **/?&lt; 0.01, ***/?&lt;0.005. [Main component symbol description] None 0 97

Claims (1)

201247612 VII. Scope of Application for Patent 1. A method for treating renal sclerosing or renal glomerulonephritis in a subject, comprising: administering an effective dose of one of the cyclohexenone compounds, a pharmaceutically acceptable salt thereof, a metabolite, a solvate thereof, or a prodrug thereof to the host, wherein the cyclohexenone compound has the following structure: Wherein each X and Y system is independently oxygen, nr5, or sulfur; R is hydrogen or CpOKVCs alkyl; each R, R2, and R3 are independently hydrogen, methyl, and bite (CH2) m-CH3; R4 is NR5R6, OR5, 〇C(=0)R7, C(=〇)〇r5, c(=〇)r5, halogen, 5 or 6 membered ring lactone, CVC8 alkyl, C2- a C8 alkenyl group, a c2-C8 alkynyl group, an aryl group, or a glucosyl group, wherein 5 or 6 membered ring lactones, alkyl groups, C2-C8 alkenyl groups, CrC8 alkynyl groups, aryl groups, and glucosyl group-selective One or more selected from the group consisting of NR5R6, or5, oc(=o)r7, C(=0)0R5, c(=〇)R5, Ci-C8 炫, C2-C8 dilute, C2-C8 block, C3 Substituting -C8 cycloalkyl, C|-C8 halogen-based, and CrC8 alkoxy substituent; each Rs, and Re are each independently hydrogen or C丨-C8 alkyl; R_7 is C|- Cg Hyun, OR5, or nr5r6; m is 1-12; and η is 1-12 » 98 201247612 2. A method of treating renal impairment or necrosis of the kidney, including: administering one of the effective doses of the ring a hexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, or a prodrug thereof thereof A main body, wherein the cyclohexenone compound had the following structure: Wherein each X and Y system is independently oxygen, NR5, or sulfur; R is hydrogen or an alkyl group; each core, R2, and R3 are each independently hydrogen, methyl, or (CH2)m-CH3 R4 is NR5R6, or5, oc(=o)r7, c(=o)or5, c(=o)r5, halogen, 5 or 6 membered ring lactone, cvc8 alkyl, C2-C8 alkenyl, C2 a -C8 alkynyl, aryl, or glucosyl group, wherein 5 or 6 membered ring lactones, CrCs alkyl groups, C2-C8 alkenyl groups, C2-C8 alkynyl groups, aryl groups, and glucosyl group-selective ones Or above selected from NR5R6, OR5, 0C(=0)R7, c(=o)or5, c(=o)r5, C|-Cg alkyl, C2-C8 dilute, C2-C8 fast radical, C3- Substituted by a C8 cycloalkyl, Ci_Cg haloalkyl, and C丨-c8 alkoxy substituent; each R5, and each independently hydrogen, or C|-C8 alkyl; RACi-Cs alkyl, hydrazine R5, or NR5R6; m is 1-12; and η is 1.-12. 99 201247612 3. A method for increasing renal cell nuclear factor-E2 correlation factor 2 (Nrf2) activity of a subject, comprising: administering an effective dose of one cyclohexenone compound, a pharmaceutically acceptable salt thereof, and metabolism thereof a substance, a solvate thereof, or a prodrug thereof to the main Zhao', wherein the cyclohexenone compound has the following structure: Wherein 'each X and Y are each independently oxygen, NR5, or sulfur; R is hydrogen, or CpCOCVCs alkyl; each Ri'R2, and R3 are each independently hydrogen, methyl, or (CH2)m -CH3 ; R4 is NR5R6, OR5, 〇C(=0)R7, C(=〇)〇R5, C(=〇)R5, halogen, 5 or 6 membered ring lactone, CVC8 alkyl, C2-C8 Alkenyl, C2-C8 block, aryl, or glucosyl' wherein '5 or 6 membered ring lactone, CrC8 alkyl, C2_C8 alkenyl, Cz-Cs alkynyl, aryl, and glucosyl selective One or more selected from the group consisting of NR5R6, OR5, 0C(=0)R7, C(=0)〇R5, c(=〇)r5, C!-C8 alkyl, C2-C8 alkenyl, c2-c8 Substituting a C3-C8 cycloalkyl group, a c-haloalkyl group, and a C!-C8 alkoxy group; each of Rs and R.6 is independently hydrogen, or c丨-c8 alkyl; R7 is C|-C8 alkyl, OR5, or NR5R_6; m is 1-12; and η is 1-12 〇100 201247612 4. Inhibition of a subject's renal NF-κΒ activity and/or transforming growth factor (TGF) - U protein expression method, comprising: administering an effective dose of one of cyclohexanone compounds, pharmaceutically acceptable salts thereof, and metabolism thereof And a solvate thereof, or a prodrug thereof to the host, wherein the cyclohexenone compound has the following structure: Wherein 'each X and Y are each independently oxygen, nr5, or sulfur; R is hydrogen, or (::(=0)(:,-0:8 alkyl; each R丨, R2, and & Each is independently hydrogen, methyl, or (CH2)m-CH3; R4 is NR5R6, OR5, 〇C(=0)R7, C(=0)0R5, C(=〇)R5, halogen, 5 Or 6-membered ring vinegar, CVCs alkyl, CrC8 alkenyl, C2-C8 alkynyl, aryl, or glucosyl, wherein 5 or 6 membered cyclic lactone, Cl_c8 alkyl, C2_C8 alkenyl, CrCg alkynyl, The aryl group and the glucose group are selectively selected from the group consisting of NR5R6, or5, 0C(=0)R7, c(=〇)〇R5, c(=〇)R5 group, c2-c8 base group, c2 Substituting -C8 block, &lt;:3-&lt;:8 cycloalkyl, C,-C{halide, and Ci-C8 alkoxy substituent; each R5, and each independently hydrogen Or C丨_C8 alkyl; R7 is C "C8 alkyl, 〇R5, or nr5r6; m is M2; and η is 1-12. 101 201247612, a method of inhibiting a ROS/ΝΟ and// Or p4 7phox is administered as an effective dose of one of the cyclohexanone compounds, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, or a precursor thereof The drug to the host 'where' the cyclohexenone compound has the following structure: Wherein 'each X and γ are each independently oxygen, Nr5, or 戚; R is hydrogen, or ¢: (=0)0, -(:8 炫; each Ri, R2, and R_3 are independent Is hydrogen, fluorenyl, or (CH2)m-CH3; R4 is NR5R6, 〇R5, 〇c(=〇)r7, c(=〇&gt;〇R5, C(=0)R5, halogen, 5 or 6-membered ring lactone, c--c8 alkyl, c2-C8 dilute, C2-C8 alkynyl, aryl, or glucosyl' wherein 5 or 6 membered cyclic lactone, crC8 alkyl, C2-C8 One or more selected from the group consisting of NR5R6, OR5, 〇c(=〇)r7, c(=〇)〇R5, C(=0)R5, Substituted by a substituent such as a pyridyl group, a C2-C8 dilute group, a (2-(8-alkynyl group, a c3-C8 cyclohexyl group, a halogen group, and a Ci-C8 methoxy group); each R5, and R6 system Each is independently hydrogen, or C1_C8; J^; R7 is Ci-C8 alkyl, OR5' or nr5r6; m is 1 -12; and η is 1-12. 102 201247612 6. A CD3+/CD69+ reducing a subject A method of T cells, comprising: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, Or a pre-drug thereof to the main section, wherein the cyclohexenone compound has the following structure: Wherein 'each X and oxime are each independently oxygen, nr5, or sulfur; R is hydrogen, or C(=0)CrC8 alkyl; each of Ri, R.2, and R_3 is independently hydrogen, Or, (CH2)m-CH3; R4 is NR5R6, OR5, 〇c(=o)r7, C(=〇)〇R5, C(=0)R5, _素' 5 or 6 membered ring lactone , C"C8 alkyl, c2-c8 alkenyl, c2-c8 alkynyl, aryl, or glucosyl, wherein 5 or 6 membered ring lactone, Ci-Cg alkyl, C2-C8 alkenyl, CrC8 alkyne The one, at least one selected from the group consisting of NR5R6, OR5, 〇C(=〇)R7, c(=〇)〇R5, C(=0)R5, C|-C8 is preferably selected from the group consisting of NR5R6, OR5, 〇C(=〇)R7, C(=〇)〇R5, Substituent, C2-C8: wpr group, c2_c8 block group, C3-C8 ring: 3⁄4 group, CVC8 halogen group, and Ci-C8 alkoxy substituent; each R5, and R6 are independently hydrogen Or Cl_C8 alkyl; R? is Ci-Cs alkyl, OR5, or NR5R6; m is 1-12; and η is 1-12. 103 201247612 7. - Raising glutathione peroxidase in the kidney ( The method of GPx) activity comprises: administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, and a solvent thereof Thereof, or a pharmaceutical predecessor to the main body, wherein the cyclohexenone compound had the following structure: Wherein 'each X and Y are each independently oxygen, NR5, or sulfur; R is hydrogen, or CbCOCi-Cs alkyl; each R, R2, and Rs are each independently hydrogen, methyl, or ( CH2)m-CH3; R4 is nr5r6, 〇r5, 〇c(=o)r7, C(=0)0R5, c(=〇)R5, dentate, 5 or 6 member vinegar, Q-Cs Affiliation, C2-C8 dilute, C2_C8 decyl, aryl, or glucosyl, wherein 5 or 6 membered vinegar, Ci_C8 alkyl, C2_C8 alkenyl, fs alkynyl, aryl, and glucosyl One or more selected from the group consisting of NR5R6, 〇r5, oc(=〇)R7, c(=〇)〇R5 c(=〇)R5 CVC8 alkyl, c2_c8 alkenyl, c2_c8 alkynyl, C3_C8 cycloalkyl, C "5C8 dentate" and a substituent of Ci-C8 alkoxy group; each R5, and R6 are each independently hydrogen or C丨·C8 alkyl; R7 is CVC8 alkyl, 〇R5, or NR5R6; ni is 1 -12; and η is 1·12. 8. A method for reducing a pro-inflammatory cytokine factor in a subject, comprising: 104 201247612 administering an effective dose of one cyclohexenone compound, its medicine Acceptable salts, metabolites, solvates thereof, or precursors thereof The drug is to the host, wherein the cyclohexenone compound has the following structure: Wherein each X and Y system is independently oxygen, NR5, or sulfur; R is hydrogen, or (:(=0)(ν&lt;:8 alkyl; each and R3 are independently argon, sulfhydryl Or (CH2)m-CH3; R4 is NR5R6, or5, oc(=o)r7, c(=〇)〇r5, c(=o)r5, tropin, 5 or 6-membered ring lactone, C , -C8 leucoyl, c2-c8 alkenyl, C2-C8 fast radical, aryl, or glucosyl, wherein '5 or 6 membered cyclic lactone, Cl-C8 alkyl, C2-C8 alkenyl, Ca-C8 Alkynyl 'aryl, and glucosyl-selective one or more selected from the group consisting of NR5R6, OR5, 〇C(=0)R7, c(=〇)〇r5, c(=0)R5, C1-C8 Substituted by a substituent of a c2-C8 dilute 'C2-C8 block group, a c3-c8 cycloalkyl group, a C|-C8 south alkyl group, and a CrC:8 alkoxy group; each R5, and R_6 system are each substituted Independently hydrogen or calcined; Rule 7 is Ci-Cg alkyl, OR5, or NR5R6; m is 1-12; and η is: Bu 12. Blisters include MCP-1, IL-6, 9. Apply The method of claim 8, wherein the proinflammatory fine JL-Ιβ, IL-18, or a combination thereof. 105 201247612 10· a reduction in the expression and/or inhibition of thiocysteine-1 in the kidney A method of renal NLRP3 activity, comprising: administering an effective dose of one of a cyclohexanone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, or a prodrug thereof to the subject, wherein the ring The hexenone compound has the following structure: Wherein each X and Y system is independently oxygen, nr5, or sulfur; R is hydrogen, or hydrazine: (=0) (:, -(:8 alkyl; each R丨, Rz, and &amp; Each is independently hydrogen, fluorenyl, or (CH2)m-CH3; R4 is NR5R6, 〇R5, 〇C(=〇)R7, c(=o)or5, c(=o)r5, halogen, 5 Or 6-membered ring lactone, C,-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, aryl, or glucosyl, wherein '5 or 6 membered ring lactone, CrCe alkyl, C2-C8 One or more selected from the group consisting of NR5R6, 〇R5, 〇C(=〇)R7, C(=0)0R5, C( =0) R5, CrC8, K2-C8 dilute, C2-C8 alkynyl, 0:3-(:8 cycloalkyl, (VC8 haloalkyl, and C,-C8 alkoxy substituent) Substituted; each Rs, and each independently hydrogen, or CpCs alkyl; alkyl, hydrazine R5, or NR5R6; m is 1 -12; and η is 1-12. 11 · One reduces renal NF-kB in the kidney A method of dosage comprising: 106 201247612 administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, or a prodrug thereof thereto A main body, wherein the cyclohexenone compound had the following structure: r, cm Wherein each X and Y system is independently oxygen, nr5, or sulfur; R is argon or (:(=0)〇ν(:8 alkyl; each R, R·2, and R3 Each is independently hydrogen, methyl, or (CH2)m-CH3; R4 is NR5R6, OR5, oc(=o)r7, C(=0)0R5, c(=〇)r5, N, 5 or 6 In the ring, vinegar, C丨-Ce Hyun, C2-C8, C2-C8 alkynyl, aryl, or glucosyl, wherein 5 or 6 membered cyclic lactone, CrCs alkyl, c2&gt; (8) alkenyl, C2_CS alkynyl, aryl, and glucosyl-selective one or more selected from NR5R6, OR5, 0C(=0)R7, C(=0)OR5, c(=〇)r5 Substituted with a substituent of c, -c8 alkyl, c2-c8 alkenyl, C2-C8 alkynyl, fluorene: 3-(:8-cycloalkyl, Ci_C8 haloalkyl, and c丨-c8 alkoxy; Each R5, and R6 is independently hydrogen or Crc8 alkyl; RtSCVCs alkyl, OR5, or NR5R6; m is: U12; and η is 1-12. 12. Method for inhibiting apoptosis in the kidney Including: 107 201247612 administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, or Huang medicament to the main trend, wherein the cyclohexenone compound had the following structure: Wherein 'each X and Y are each independently oxygen, nr5, or sulfur; R is hydrogen, or CpCOCi-Ce alkyl; each Ri, R2, and R3 are each independently hydrogen, methyl, or (CH2) m-CH3; R4 is NR5R6, 〇R5, 〇c(=〇)r7, c(=〇)OR5, c(=o)r5, dentate, 5 or 6 membered ring lactone, C"C8 alkane a C2-C8 alkenyl group, a C2-C8 alkynyl group, an aryl group, or a glucosyl group, wherein 5 or 6 membered ring lactones, CrCs alkyl groups, C2-C8 alkenyl groups, CrC8 alkynyl groups, aryl groups, and glucose One or more selected from the group consisting of NR5R6, 〇R5, 〇c(=0)r7, c(=〇)〇R5, C(=0)R5, CrC*alkyl-C2-C8, Substituting C: rC8 alkynyl, c3-c8 cyclodextrin, q-Cs haloalkyl, and Ci-Ce alkoxy; each R5, and Re are independently hydrogen, or C丨_C8 Alkyl; R? is Cl_C8, 〇R5, or nr5r6; m is 1 -12; and η is 1 -12 β or glomerulonephritis method 13 ·-protection or prevention of a kidney Ball sclerosis and / Including: 108 201247612 Administration of an effective dose of one of the cyclohexenone compounds, their pharmaceutically acceptable salts, their generation Thereof, solvate thereof, or the precursor drugs to the main body 'to reduce kidney TGF-βΙ proteins levels of expression and collagen I, ΠΙ and IV protein aggregation' wherein the cyclohexenone compound had the following structure: Wherein 'each X and oxime are each independently oxygen, NR5' or sulfur; R is hydrogen or CpOKVCe alkyl; each R丨, R2, and R3 are each independently hydrogen, methyl, or (CH2) m-CH3 ; R4 is NR5R6, 〇R5, 〇c(=〇)R7, c(=o)or5, c(=o)r5, halogen, 5 or 6 membered ring lactone, CrCs alkyl, c2- C8 dilute, C2-C8 alkynyl, aryl, or glucosyl, wherein '5 or 6 membered ring lactone, C^-Ce alkyl, C2-C8 alkenyl, C2_CS alkynyl, aryl, and glucosyl Selectively one or more selected from the group consisting of NR5R6, 〇R5, 〇C(=〇)R7, c(=o)or5, c(=o)r5, yl, c2-c8, and c2-c8 And a substituent of a c3-c8 cycloalkyl group, (a VC8 halogen group, and a C丨-C8 alkoxy group; each Rs and a system are independently hydrogen or a Cl_C8 alkyl group; 1^7 is a € 1-08 alkyl, 〇115, or >11151^6; m is 1-12; and η is: 1-12. 14. A method for treating a subject with local squamous sclerosis (FsgS) 2 Including: 109 201247612 administering an effective dose of one of cyclohexenone compounds, pharmaceutically acceptable salts thereof, metabolites thereof, and solvation thereof Or a pre-drug to the subject, (i) increasing Nrf2 activity and/or (ii) inhibiting NF-icB-related inflammatory response in the kidney and TGF-βΙ-induced fibrosis, wherein the cyclohexenone compound is Has the following structure: Wherein each X and Y system is independently oxygen, NR5, or sulfur; R is hydrogen or CbCOCi-Cs alkyl; each of Ri, R2, and R_3 is independently nitrogen, sulfhydryl, or (CH2) m-CH3 ; R4 is NR5R6, 〇R5, 〇c(=〇)r7 'c(=〇)〇r5, c(=〇)R5, pheromone, 5 or 6 member vinegar, Cl_(:8 An alkyl group, a c2_C8 dilute group, a c2_C8 fast group, an aryl group, or a glucosyl group, wherein 5 or 6 membered ring lactones, Ci_C8 alkyl groups, C2_c8 alkenyl groups, Cz-C8 alkynyl groups, aryl groups, and glucosyl group selection One or more selected from the group consisting of NR5R6, 〇R5' 〇c(=〇)r7, c 〇)〇R5, c(=〇)r5, c,-c8 alkyl, c2-c8 alkenyl, c2- Substituted by a C8 alkynyl group, a c3 c8 cycloalkyl group, a C|_C8 haloalkyl group, and a Ci-C8 alkoxy group; each of R5 and R0 is independently hydrogen or an alkyl group; R5, or nr5r6; m is 1 -12; and η is 1 -12. 15. A method of treating a subject-derived glomerulonephritis comprising: 201247612 administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, a metabolite thereof, a solvate thereof, or a precursor thereof The drug is administered to the host to (1) inhibit renal NLRP3 inflammatory body activation and/or (Π) inhibit the increase in butyl cell activity, wherein the cyclohexenone compound has the following structure: Wherein 'each X and Y are each independently oxygen, NR5, or sulfur; R is hydrogen, or CpC^CVCs alkyl; each R, R2, and R3 are each independently hydrogen, sulfhydryl, or ( Cn2)m-CR3; R4 is NR5R6, 〇R5, 〇C(=〇)R7, C(=0)〇R5, c(=〇)r5, alizarin, 5 or 6 membered ring lactone, CVC8 alkane , C2-C8 alkenyl, C2-c8 alkynyl, aryl, or glucosyl' wherein 5 or 6 membered cyclic lactone, C-C8 alkyl, c2-C8 dilute, Ci-C: 8 The one, at least one selected from the group consisting of NR5R6, 〇R5, 〇c(=〇)R7, C(=0)0R5, c(=〇)r5, &lt;^-0 :8, substituted by a C2-C8 dilute group, a C2-C8 alkynyl group, a C3-C8 cyclopentyl group, a CVCs haloalkyl group, and a C"C8 alkoxy group; each Rs, and an anaesthetic 6 system Each is independently hydrogen or a CrC8 alkyl group; R7 is a C丨-C8 alkyl group, 〇r5, or nr5r6; m is: 1·12; and η is 〖-12. 16. - an immunoglobulin that slows down a subject A method of type A glomerulonephritis (IgAN), comprising: 201247612 administering an effective dose of one of a cyclohexenone compound, a pharmaceutically acceptable salt thereof, and a metabolite thereof Solvate thereof, or a pharmaceutical predecessor to the main body of 'where' the cyclohexenone compound had the following structure: Wherein 'each X and Y are each independently oxygen, nr5, or sulfur; R is hydrogen, or c(=0)cvc8 alkyl; each of Ri, R2, and R3 is independently argon, sulfhydryl, (CH2)m-CH3; R4 is NR5R6, OR5, oc(=o)r7, c(=o)or5, c(=0)R5, halogen, 5 or 6 membered ring lactone, alkyl group, c2 a -c8 dilute group, a C2-C8 alkynyl group, an aryl group, or a glucosyl group, wherein 5 or 6 membered ring lactones, C,-C8 alkyl groups, C2-C8 alkenyl groups, Cz-C8 alkynyl groups, aryl groups, And a glucose-based selective one or more selected from the group consisting of NR5R6, or5, 〇c(=o)r7, c(=o)or5, C(=0)R5, Crc8 alkyl, c2-c8 alkenyl, C2 Substituted by a substituent of -C8 alkynyl, C3-C8 cycloalkyl, CrCs haloalkyl, and c丨-c8 alkoxy; each R5, and R6 are each independently hydrogen or Crc8 alkyl; R7 Ci-C8 alkyl, OR5, or NR5R6; m is 1-12; and η is 1-12. 17. The method of claim 1, wherein the glomerulosclerosis is local glomerulosclerosis (FSGS) or nodular glomerular sclerosis. The method of claim 1, wherein the glomerulosclerosis is localized glomerulosclerosis (FSGS). 19. The method according to claim 1, wherein the glomerulonephritis is an immunoglobulin type A glomerulonephritis (IgAN). The method of claim 1, wherein The cyclohexenone compound prevents oxidation stress. 21. The method of claim 20, wherein the oxidative stress is prevented by reducing TGF-[beta] and extracellular matrix protein expression. 22. The method of claim 1, wherein the cyclohexene oxime compound reduces CD3+/CD69+ T cells and pro-inflammatory cytokines in the subject. The method of claim 22, wherein the pro-inflammatory cytokine comprises MCP-1, IL-6, IL-Ιβ, IL-18, or a combination thereof. [24] The method of claim 2, wherein the renal sac damage comprises epithelial hyperplasia (EPHL). 25. The method of any one of claims 1 to 24, wherein the compound is isolated from Antrodia camphorata. The method of any one of claims 1 to 25, wherein R is hydrogen or c(=o)ch3. The method of any one of claims 1 to 26, wherein the Ri is hydrogen or a methyl group. 28. The method according to any one of claims 1 to 27, wherein R2 in the bean is gas or methyl. </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; 30. The method of any one of claims 1 to 29 The method according to any one of claims 1 to 30, wherein the main system is a human. Eight, schema (see next page):